Imbalances in the formation and clearance of reactive oxygen species (ROS) can lead to oxidative stress and subsequent changes that affect all aspects of physiology. To limit and repair the damage generated by ROS, cells have developed a multitude of responses. A hallmark of these responses is the activation of signaling pathways that modulate the function of downstream targets in different cellular locations. To this end, critical steps of the stress response that occur in the nucleus and cytoplasm have to be coordinated, which makes the proper communication between both compartments mandatory. Here, we discuss the interdependence of ROS-mediated signaling and the transport of macromolecules across the nuclear envelope. We highlight examples of oxidant-dependent nuclear trafficking and describe the impact of oxidative stress on the transport apparatus. Our paper concludes by proposing a cellular circuit of ROS-induced signaling, nuclear transport and repair. 1. Introduction 1.1. Reactive Oxygen Species Oxidative stress is generated by an increase in reactive oxygen species (ROS), either in the form of free radicals or nonradical oxidants [1, 2]. Although elevated levels of ROS can damage a wide variety of molecules, ROS production is essential to normal cell physiology [3–12]. As such, ROS participate in cell-signaling events and can function as second messengers. Moreover, ROS are generated at sites of inflammation, where they fend off microbial infections [13–16]. On the other hand, ROS are believed to contribute to aging [3–9, 12]; they are also produced in response to environmental insults, such as X-rays, UV light, ultrasound, or microwave radiation [17–19]. At the cellular level, ROS are generated as metabolic byproducts of normal biological processes, with oxidative phosphorylation in mitochondria as the primary source in eukaryotic cells [20]. Aside from the mitochondrial electron transport chain, NADPH oxidases, cyclooxygenases, lipoxygenases, xanthine oxidase, and other cellular enzymes make also important contributions to cellular ROS production [21–25]. The different types of ROS and their mode of action have been discussed in detail [1, 11, 26–30]. ROS that are particularly important to cell physiology include the hydroxyl radical ？OH, superoxide anion ？ O 2 ？ , the nonradical hydrogen peroxide (H2O2), alkoxy and peroxy radicals, hypochlorous acid or peroxynitrite, and reactive sulfur species [1, 29, 31, 32]. Here, we recapitulate the properties of those ROS only that are relevant to the experiments discussed in this review. The hydroxyl
References
[1]
D. P. Jones, “Radical-free biology of oxidative stress,” The American Journal of Physiology—Cell Physiology, vol. 295, no. 4, pp. C849–C868, 2008.
[2]
B. Halliwell, “Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment,” Drugs & Aging, vol. 18, no. 9, pp. 685–716, 2001.
[3]
D.-F. Dai and P. S. Rabinovitch, “Cardiac aging in mice and humans: the role of mitochondrial oxidative stress,” Trends in Cardiovascular Medicine, vol. 19, no. 7, pp. 213–220, 2009.
[4]
J. Li and N. J. Holbrook, “Common mechanisms for declines in oxidative stress tolerance and proliferation with aging,” Free Radical Biology and Medicine, vol. 35, no. 3, pp. 292–299, 2003.
[5]
T. Finkel and N. J. Holbrook, “Oxidants, oxidative stress and the biology of ageing,” Nature, vol. 408, no. 6809, pp. 239–247, 2000.
[6]
N. J. Holbrook and S. Ikeyama, “Age-related decline in cellular response to oxidative stress: links to growth factor signaling pathways with common defects,” Biochemical Pharmacology, vol. 64, no. 5-6, pp. 999–1005, 2002.
[7]
M. C. Haigis and B. A. Yankner, “The aging stress response,” Molecular Cell, vol. 40, no. 2, pp. 333–344, 2010.
[8]
A. Y. Seo, A.-M. Joseph, D. Dutta, J. C. Y. Hwang, J. P. Aris, and C. Leeuwenburgh, “New insights into the role of mitochondria in aging: mitochondrial dynamics and more,” Journal of Cell Science, vol. 123, no. 15, pp. 2533–2542, 2010.
[9]
K. C. Kregel and H. J. Zhang, “An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations,” The American Journal of Physiology—Regulatory Integrative and Comparative Physiology, vol. 292, no. 1, pp. R18–R36, 2007.
[10]
P. Storz, “Forkhead homeobox type O transcription factors in the responses to oxidative stress,” Antioxidants & Redox Signaling, vol. 14, no. 4, pp. 593–605, 2011.
[11]
W. Dr？ge, “Free radicals in the physiological control of cell function,” Physiological Reviews, vol. 82, no. 1, pp. 47–95, 2002.
[12]
W. Dr？ge and H. M. Schipper, “Oxidative stress and aberrant signaling in aging and cognitive decline,” Aging Cell, vol. 6, no. 3, pp. 361–370, 2007.
[13]
H.-C. Yang, M.-L. Cheng, H.-Y. Ho, and D. Tsun-Yee Chiu, “The microbicidal and cytoregulatory roles of NADPH oxidases,” Microbes and Infection, vol. 13, no. 2, pp. 109–120, 2010.
[14]
B. M. Babior, “NADPH oxidase: an update,” Blood, vol. 93, no. 5, pp. 1464–1476, 1999.
[15]
M. Reth, “Hydrogen peroxide as second messenger in lymphocyte activation,” Nature Immunology, vol. 3, no. 12, pp. 1129–1134, 2002.
[16]
M. Valko, D. Leibfritz, J. Moncol, M. T. D. Cronin, M. Mazur, and J. Telser, “Free radicals and antioxidants in normal physiological functions and human disease,” The International Journal of Biochemistry & Cell Biology, vol. 39, no. 1, pp. 44–84, 2007.
[17]
R. Pallela, Y. Na-Young, and S.-K. Kim, “Anti-photoaging and photoprotective compounds derived from marine organisms,” Marine Drugs, vol. 8, no. 4, pp. 1189–1202, 2010.
[18]
A. J. Ridley, J. R. Whiteside, T. J. McMillan, and S. L. Allinson, “Cellular and sub-cellular responses to UVA in relation to carcinogenesis,” International Journal of Radiation Biology, vol. 85, no. 3, pp. 177–195, 2009.
[19]
K. Dittmann, C. Mayer, R. Kehlbach, M. C. Rothmund, and H. P. Rodemann, “Radiation-induced lipid peroxidation activates src kinase and triggers nuclear EGFR transport,” Radiotherapy & Oncology, vol. 92, no. 3, pp. 379–382, 2009.
[20]
M. Rigoulet, E. D. Yoboue, and A. Devin, “Mitochondrial ROS generation and its regulation: mechanisms involved in H2O2 signaling,” Antioxidants & Redox Signaling, vol. 14, no. 3, pp. 459–468, 2011.
[21]
K.-J. Cho, J.-M. Seo, and J.-H. Kim, “Bioactive lipoxygenase metabolites stimulation of NADPH oxidases and reactive oxygen species,” Molecules and Cells, vol. 32, no. 1, pp. 1–5, 2011.
[22]
R. P. Brandes, N. Weissmann, and K. Schr？der, “NADPH oxidases in cardiovascular disease,” Free Radical Biology & Medicine, vol. 49, no. 5, pp. 687–706, 2010.
[23]
T. M. Paravicini and R. M. Touyz, “NADPH oxidases, reactive oxygen species, and hypertension,” Diabetes Care, vol. 31, supplement 2, pp. S170–S180, 2008.
[24]
F. Jiang, Y. Zhang, and G. J. Dusting, “NADPH oxidase-mediated redox signaling: roles in cellular stress response, stress tolerance, and tissue repair,” Pharmacological Reviews, vol. 63, no. 1, pp. 218–242, 2011.
[25]
A. A. Fatokun, T. W. Stone, and R. A. Smith, “Oxidative stress in neurodegeneration and available means of protection,” Frontiers in Bioscience, vol. 13, no. 9, pp. 3288–3311, 2008.
[26]
V. Calabrese, C. Cornelius, A. T. Dinkova-Kostova, E. J. Calabrese, and M. P. Mattson, “Cellular stress responses, the hormesis paradigm, and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders,” Antioxidants & Redox Signaling, vol. 13, no. 11, pp. 1763–1811, 2010.
[27]
J. D. Acharya and S. S. Ghaskadbi, “Islets and their antioxidant defense,” Islets, vol. 2, no. 4, pp. 225–235, 2010.
[28]
S. V. Avery, “Molecular targets of oxidative stress,” Biochemical Journal, vol. 434, no. 2, pp. 201–210, 2011.
[29]
I. Dalle-Donne, A. Scaloni, D. Giustarini et al., “Proteins as biomarkers of oxidative/nitrosative stress in diseases: the contribution of redox proteomics,” Mass Spectrometry Reviews, vol. 24, no. 1, pp. 55–99, 2005.
[30]
B. Halliwell, “Oxidative stress and neurodegeneration: where are we now?” Journal of Neurochemistry, vol. 97, no. 6, pp. 1634–1658, 2006.
[31]
G. I. Giles and C. Jacob, “Reactive sulfur species: an emerging concept in oxidative stress,” Biological Chemistry, vol. 383, no. 3-4, pp. 375–388, 2002.
[32]
R. P. Guttmann, “Redox regulation of cysteine-dependent enzymes,” Journal of Animal Science, vol. 88, no. 4, pp. 1297–1306, 2010.
[33]
A. Colquhoun, “Lipids, mitochondria and cell death: implications in neuro-oncology,” Molecular Neurobiology, vol. 42, no. 1, pp. 76–88, 2010.
[34]
L. M. Sayre, G. Perry, and M. A. Smith, “Oxidative stress and neurotoxicity,” Chemical Research in Toxicology, vol. 21, no. 1, pp. 172–188, 2008.
[35]
M. P. Czubryt, J. A. Austria, and G. N. Pierce, “Hydrogen peroxide inhibition of nuclear protein import is mediated by the mitogen-activated protein kinase, ERK2,” The Journal of Cell Biology, vol. 148, no. 1, pp. 7–16, 2000.
[36]
B. Halliwell, M. V. Clement, and L. H. Long, “Hydrogen peroxide in the human body,” FEBS Letters, vol. 486, no. 1, pp. 10–13, 2000.
[37]
J. A. Imlay, “Cellular defenses against superoxide and hydrogen peroxide,” Annual Review of Biochemistry, vol. 77, no. 1, pp. 755–776, 2008.
[38]
U. Stochaj, R. Rassadi, and J. Chiu, “Stress-mediated inhibition of the classical nuclear protein import pathway and nuclear accumulation of the small GTPase Gsp1p,” The FASEB Journal, vol. 14, no. 14, pp. 2130–2132, 2000.
[39]
M. Kodiha, A. Chu, N. Matusiewicz, and U. Stochaj, “Multiple mechanisms promote the inhibition of classical nuclear import upon exposure to severe oxidative stress,” Cell Death & Differentiation, vol. 11, no. 8, pp. 862–874, 2004.
[40]
Y. Miyamoto, T. Saiwaki, J. Yamashita et al., “Cellular stresses induce the nuclear accumulation of importin α and cause a conventional nuclear import block,” The Journal of Cell Biology, vol. 165, no. 5, pp. 617–623, 2004.
[41]
S. Boisnard, G. Lagniel, C. Garmendia-Torres et al., “H2O2 activates the nuclear localization of Msn2 and Maf1 through thioredoxins in Saccharomyces cerevisiae,” Eukaryotic Cell, vol. 8, no. 9, pp. 1429–1438, 2009.
[42]
J. Song, J. Li, J. Qiao, S. Jain, B. M. Evers, and D. H. Chung, “PKD prevents H2O2-induced apoptosis via NF-κB and p38 MAPK in RIE-1 cells,” Biochemical and Biophysical Research Communications, vol. 378, no. 3, pp. 610–614, 2009.
[43]
M. L. Circu and T. Y. Aw, “Reactive oxygen species, cellular redox systems, and apoptosis,” Free Radical Biology and Medicine, vol. 48, no. 6, pp. 749–762, 2010.
[44]
S. Lenzen, “Oxidative stress: the vulnerable β-cell,” Biochemical Society Transactions, vol. 36, no. 3, pp. 343–347, 2008.
[45]
B. van Loon, E. Markkanen, and U. Hübscher, “Oxygen as a friend and enemy: how to combat the mutational potential of 8-oxo-guanine,” DNA Repair, vol. 9, no. 6, pp. 604–616, 2010.
[46]
B. Halliwell, “Free radicals and antioxidants—quo vadis?” Trends in Pharmacological Sciences, vol. 32, no. 3, pp. 125–130, 2011.
[47]
J. L. Evans, I. D. Goldfine, B. A. Maddux, and G. M. Grodsky, “Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes,” Endocrine Reviews, vol. 23, no. 5, pp. 599–622, 2002.
[48]
K. Jomova, D. Vondrakova, M. Lawson, and M. Valko, “Metals, oxidative stress and neurodegenerative disorders,” Molecular and Cellular Biochemistry, vol. 345, no. 1-2, pp. 91–104, 2010.
[49]
F. Giacco and M. Brownlee, “Oxidative stress and diabetic complications,” Circulation Research, vol. 107, no. 9, pp. 1058–1070, 2010.
[50]
J. Ren, L. Pulakat, A. Whaley-Connell, and J. R. Sowers, “Mitochondrial biogenesis in the metabolic syndrome and cardiovascular disease,” Journal of Molecular Medicine, vol. 88, no. 10, pp. 993–1001, 2010.
[51]
R. Stanton, “Oxidative stress and diabetic kidney disease,” Current Diabetes Reports, vol. 11, no. 4, pp. 330–336, 2011.
[52]
C. K. Roberts and K. K. Sindhu, “Oxidative stress and metabolic syndrome,” Life Sciences, vol. 84, no. 21-22, pp. 705–712, 2009.
[53]
S. Chrissobolis, A. A. Miller, G. R. Drummond, B. K. Kemp-Harper, and C. G. Sobey, “Oxidative stress and endothelial dysfunction in cerebrovascular disease,” Frontiers in Bioscience, vol. 16, no. 5, pp. 1733–1745, 2011.
[54]
J. C. Jonas, M. Bensellam, J. Duprez, H. Elouil, Y. Guiot, and S. M. A. Pascal, “Glucose regulation of islet stress responses and β-cell failure in type 2 diabetes,” Diabetes, Obesity & Metabolism, vol. 11, supplement 4, pp. 65–81, 2009.
[55]
J. L. Rains and S. K. Jain, “Oxidative stress, insulin signaling, and diabetes,” Free Radical Biology and Medicine, vol. 50, no. 5, pp. 567–575, 2011.
[56]
S. Reuter, S. C. Gupta, M. M. Chaturvedi, and B. B. Aggarwal, “Oxidative stress, inflammation, and cancer: how are they linked?” Free Radical Biology and Medicine, vol. 49, no. 11, pp. 1603–1616, 2010.
[57]
Y. S. Kanwar, J. Wada, L. Sun et al., “Diabetic nephropathy: mechanisms of renal disease progression,” Experimental Biology and Medicine, vol. 233, no. 1, pp. 4–11, 2008.
[58]
A. Tojo, K. Asaba, and M. L. Onozato, “Suppressing renal NADPH oxidase to treat diabetic nephropathy,” Expert Opinion on Therapeutic Targets, vol. 11, no. 8, pp. 1011–1018, 2007.
[59]
P. Diaz Vivancos, T. Wolff, J. Markovic, F. V. Pallardó, and C. H. Foyer, “A nuclear glutathione cycle within the cell cycle,” Biochemical Journal, vol. 431, no. 2, pp. 169–178, 2010.
[60]
H. R. López-Mirabal and J. R. Winther, “Redox characteristics of the eukaryotic cytosol,” Biochimica et Biophysica Acta—Molecular Cell Research, vol. 1783, no. 4, pp. 629–640, 2008.
[61]
D. P. Jones and Y. M. Go, “Redox compartmentalization and cellular stress,” Diabetes, Obesity and Metabolism, vol. 12, no. 2, pp. 116–125, 2010.
[62]
é. Margittai and R. Sitia, “Oxidative protein folding in the secretory pathway and redox signaling across compartments and cells,” Traffic, vol. 12, no. 1, pp. 1–8, 2011.
[63]
O. Blokhina, E. Virolainen, and K. V. Fagerstedt, “Antioxidants, oxidative damage and oxygen deprivation stress: a review,” Annals of Botany, vol. 91, pp. 179–194, 2003.
[64]
T. Fukai and M. Ushio-Fukai, “Superoxide dismutases: role in redox signaling, vascular function and diseases,” Antioxidants & Redox Signaling, vol. 15, no. 6, pp. 1583–1606, 2011.
[65]
A. Valdivia, S. Pérez-álvarez, J. D. Aroca-Aguilar, I. Ikuta, and J. Jordán, “Superoxide dismutases: a physiopharmacological update,” Journal of Physiology & Biochemistry, vol. 65, no. 2, pp. 195–208, 2009.
[66]
H. Jefferies, J. Coster, A. Khalil, J. Bot, R. D. McCauley, and J. C. Hall, “Glutathione,” ANZ Journal of Surgery, vol. 73, no. 7, pp. 517–522, 2003.
[67]
N. S. Dhalla, A. B. Elmoselhi, T. Hata, and N. Makino, “Status of myocardial antioxidants in ischemia-reperfusion injury,” Cardiovascular Research, vol. 47, no. 3, pp. 446–456, 2000.
[68]
D. M. Townsend, K. D. Tew, and H. Tapiero, “The importance of glutathione in human disease,” Biomedicine & Pharmacotherapy, vol. 57, no. 3-4, pp. 145–155, 2003.
[69]
M. Kodiha, D. Tran, C. Qian et al., “Oxidative stress mislocalizes and retains transport factor importin-α and nucleoporins Nup153 and Nup88 in nuclei where they generate high molecular mass complexes,” Biochimica et Biophysica Acta—Molecular Cell Research, vol. 1783, no. 3, pp. 405–418, 2008.
[70]
K. Weis, “Regulating access to the genome: nucleocytoplasmic transport throughout the cell cycle,” Cell, vol. 112, no. 4, pp. 441–451, 2003.
[71]
S. R. Wente and M. P. Rout, “The nuclear pore complex and nuclear transport,” Cold Spring Harbor Perspectives in Biology, vol. 2, no. 10, pp. 1–19, 2010.
[72]
M. Kodiha, N. Crampton, S. Shrivastava, R. Umar, and U. Stochaj, “Traffic control at the nuclear pore,” Nucleus, vol. 1, no. 3, pp. 237–244, 2010.
[73]
I. K. H. Poon and D. A. Jans, “Regulation of nuclear transport: central role in development and transformation?” Traffic, vol. 6, no. 3, pp. 173–186, 2005.
[74]
S. A. Adam, “The nuclear transport machinery in Caenorhabditis elegans: a central role in morphogenesis,” Seminars in Cell & Developmental Biology, vol. 20, no. 5, pp. 576–581, 2009.
[75]
D. Adam Mason and D. S. Goldfarb, “The nuclear transport machinery as a regulator of Drosophila development,” Seminars in Cell & Developmental Biology, vol. 20, no. 5, pp. 582–589, 2009.
[76]
S. Hutten and R. H. Kehlenbach, “CRM1-mediated nuclear export: to the pore and beyond,” Trends in Cell Biology, vol. 17, no. 4, pp. 193–201, 2007.
[77]
N. Kudo, N. Matsumori, H. Taoka et al., “Leptomycin B inactivates CRM1/exportin 1 by covalent modification at a cysteine residue in the central conserved region,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 16, pp. 9112–9117, 1999.
[78]
D. A. Jans, C.-Y. Xiao, and M. H. C. Lam, “Nuclear targeting signal recognition: a key control point in nuclear transport?” BioEssays, vol. 22, no. 6, pp. 532–544, 2000.
[79]
N. Crampton, M. Kodiha, S. Shrivastava, R. Umar, and U. Stochaj, “Oxidative stress inhibits nuclear protein export by multiple mechanisms that target FG nucleoporins and Crm1,” Molecular Biology of the Cell, vol. 20, no. 24, pp. 5106–5116, 2009.
[80]
M. J. Morgan and Z. G. Liu, “Crosstalk of reactive oxygen species and NF-κB signaling,” Cell Research, vol. 21, no. 1, pp. 103–115, 2011.
[81]
P. Ak and A. J. Levine, “p53 and NF-κB: different strategies for responding to stress lead to a functional antagonism,” The FASEB Journal, vol. 24, no. 10, pp. 3643–3652, 2010.
[82]
V. P. Patel and C. T. Chu, “Nuclear transport, oxidative stress, and neurodegeneration,” International Journal of Clinical and Experimental Pathology, vol. 4, no. 3, pp. 215–229, 2011.
[83]
A. Giudice, C. Arra, and M. C. Turco, “Review of molecular mechanisms involved in the activation of the Nrf2-ARE signaling pathway by chemopreventive agents,” Methods in Molecular Biology, vol. 647, pp. 37–74, 2010.
[84]
A. Martín-Montalvo, J. M. Villalba, P. Navas, and R. de Cabo, “NRF2, cancer and calorie restriction,” Oncogene, vol. 30, no. 5, pp. 505–520, 2010.
[85]
M. Theodore, Y. Kawai, J. Yang et al., “Multiple nuclear localization signals function in the nuclear import of the transcription factor Nrf2,” Journal of Biological Chemistry, vol. 283, no. 14, pp. 8984–8994, 2008.
[86]
A. K. Jain, D. A. Bloom, and A. K. Jaiswal, “Nuclear import and export signals in control of Nrf2,” Journal of Biological Chemistry, vol. 280, no. 32, pp. 29158–29168, 2005.
[87]
D. Tang, R. Kang, H. J. Zeh, and M. T. Lotze, “High-mobility group box 1, oxidative stress, and disease,” Antioxidants & Redox Signaling, vol. 14, no. 7, pp. 1315–1335, 2011.
[88]
C. Tristan, N. Shahani, T. W. Sedlak, and A. Sawa, “The diverse functions of GAPDH: views from different subcellular compartments,” Cellular Signalling, vol. 23, no. 2, pp. 317–323, 2011.
[89]
T. Bonaldi, F. Talamo, P. Scaffidi et al., “Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion,” The EMBO Journal, vol. 22, no. 20, pp. 5551–5560, 2003.
[90]
H. Y. Ju and J.-S. Shin, “Nucleocytoplasmic shuttling of HMGB1 is regulated by phosphorylation that redirects it toward secretion,” The Journal of Immunology, vol. 177, no. 11, pp. 7889–7897, 2006.
[91]
D. Tang, Y. Shi, R. Kang et al., “Hydrogen peroxide stimulates macrophages and monocytes to actively release HMGB1,” Journal of Leukocyte Biology, vol. 81, no. 3, pp. 741–747, 2007.
[92]
K. Hayakawa, K. Arai, and E. H. Lo, “Role of ERK MAP kinase and CRM1 in IL-1β-stimulated release of HMGB1 from cortical astrocytes,” Glia, vol. 58, no. 8, pp. 1007–1015, 2010.
[93]
D. A. Butterfield, S. S. Hardas, and M. L. B. Lange, “Oxidatively modified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and Alzheimer's disease: many pathways to neurodegeneration,” Journal of Alzheimer's Disease, vol. 20, no. 2, pp. 369–393, 2010.
[94]
S. Azam, N. Jouvet, A. Jilani et al., “Human glyceraldehyde-3-phosphate dehydrogenase plays a direct role in reactivating oxidized forms of the DNA repair enzyme APE1,” Journal of Biological Chemistry, vol. 283, no. 45, pp. 30632–30641, 2008.
[95]
M. R. Hara, M. B. Cascio, and A. Sawa, “GAPDH as a sensor of NO stress,” Biochimica et Biophysica Acta, vol. 1762, no. 5, pp. 502–509, 2006.
[96]
H. J. Kwon, J. H. Rhim, I. S. Jang, G. E. Kim, S. C. Park, and E. J. Yeo, “Activation of AMP-activated protein kinase stimulates the nuclear localization of glyceraldehyde 3-phosphate dehydrogenase in human diploid fibroblasts,” Experimental & Molecular Medicine, vol. 42, no. 4, pp. 254–269, 2010.
[97]
S. Madsen-Bouterse, G. Mohammad, and R. A. Kowluru, “Glyceraldehyde-3-phosphate dehydrogenase in retinal microvasculature: implications for the development and progression of diabetic retinopathy,” Investigative Ophthalmology & Visual Science, vol. 51, no. 3, pp. 1765–1772, 2010.
[98]
H. Nakajima, W. Amano, T. Kubo et al., “Glyceraldehyde-3-phosphate dehydrogenase aggregate formation participates in oxidative stress-induced cell death,” Journal of Biological Chemistry, vol. 284, no. 49, pp. 34331–34341, 2009.
[99]
M. A. Ortiz-Ortiz, J. M. Morán, L. M. Ruiz-Mesa, J. M. B. Pedro, and J. M. Fuentes, “Paraquat exposure induces nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the activation of the nitric oxide-GAPDH-Siah cell death cascade,” Toxicological Sciences, vol. 116, no. 2, pp. 614–622, 2010.
[100]
J. Park, D. Han, K. Kim, Y. Kang, and Y. Kim, “O-GlcNAcylation disrupts glyceraldehyde-3-phosphate dehydrogenase homo-tetramer formation and mediates its nuclear translocation,” Biochimica et Biophysica Acta, vol. 1794, no. 2, pp. 254–262, 2009.
[101]
M. Ventura, F. Mateo, J. Serratosa et al., “Nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase is regulated by acetylation,” The International Journal of Biochemistry & Cell Biology, vol. 42, no. 10, pp. 1672–1680, 2010.
[102]
N. E. Zachara, N. O'Donnell, W. D. Cheung, J. J. Mercer, J. D. Marth, and G. W. Hart, “Dynamic O-GlcNAc modification of nucleocytoplasmic proteins in response to stress,” Journal of Biological Chemistry, vol. 279, no. 29, pp. 30133–30142, 2004.
[103]
A. Martínez, M. Portero-Otin, R. Pamplona, and I. Ferrer, “Protein targets of oxidative damage in human neurodegenerative diseases with abnormal protein aggregates,” Brain Pathology, vol. 20, no. 2, pp. 281–297, 2010.
[104]
M. T. Lin and M. F. Beal, “Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases,” Nature, vol. 443, no. 7113, pp. 787–795, 2006.
[105]
J. P. Morrison, M. C. Coleman, E. S. Aunan, S. A. Walsh, D. R. Spitz, and K. C. Kregel, “Aging reduces responsiveness to BSO- and heat stress-induced perturbations of glutathione and antioxidant enzymes,” The American Journal of Physiology—Regulatory Integrative & Comparative Physiology, vol. 289, no. 4, pp. R1035–R1041, 2005.
[106]
D. K. Singh, P. Winocour, and K. Farrington, “Oxidative stress in early diabetic nephropathy: fueling the fire,” Nature Reviews Endocrinology, vol. 7, no. 3, pp. 176–184, 2010.
[107]
P. M. P. Balakumar, M. K. M. Arora, J. M. Reddy, and M. B. P. Anand-Srivastava, “Pathophysiology of diabetic nephropathy: involvement of multifaceted signalling mechanism,” Journal of Cardiovascular Pharmacology, vol. 54, no. 2, pp. 129–138, 2009.
[108]
M. Brownlee, “The pathobiology of diabetic complications,” Diabetes, vol. 54, no. 6, pp. 1615–1625, 2005.
[109]
T. Nishikawa, D. Edelstein, X. L. Du et al., “Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage,” Nature, vol. 404, no. 6779, pp. 787–790, 2000.
[110]
X. Cheng, R. C. M. Siow, and G. E. Mann, “Impaired redox signaling and antioxidant gene expression in endothelial cells in diabetes: a role for mitochondria and the nuclear factor-E2-related factor 2-Kelch-like ECH-associated protein 1 defense pathway,” Antioxidants & Redox Signaling, vol. 14, no. 3, pp. 469–487, 2011.
[111]
M. Brownlee, “Biochemistry and molecular cell biology of diabetic complications,” Nature, vol. 414, no. 6865, pp. 813–820, 2001.
[112]
R. G. Baker, M. S. Hayden, and S. Ghosh, “NF-κB, inflammation, and metabolic disease,” Cell Metabolism, vol. 13, no. 1, pp. 11–22, 2011.
[113]
M. Kodiha, P. Bański, D. Ho-Wo-Cheong, and U. Stochaj, “Dissection of the molecular mechanisms that control the nuclear accumulation of transport factors importin-α and CAS in stressed cells,” Cellular & Molecular Life Sciences, vol. 65, no. 11, pp. 1756–1767, 2008.
[114]
M. Kodiha, P. Bański, and U. Stochaj, “Interplay between MEK and PI3 kinase signaling regulates the subcellular localization of protein kinases ERK1/2 and Akt upon oxidative stress,” FEBS Letters, vol. 583, no. 12, pp. 1987–1993, 2009.
[115]
M. Kodiha, A. Chu, O. Lazrak, and U. Stochaj, “Stress inhibits nucleocytoplasmic shuttling of heat shock protein hsc70,” The American Journal of Physiology—Cell Physiology, vol. 289, no. 4, pp. C1034–C1041, 2005.
[116]
M. Kodiha, J. G. Rassi, C. M. Brown, and U. Stochaj, “Localization of AMP kinase is regulated by stress, cell density, and signaling through the MEK→ERK1/2 pathway,” The American Journal of Physiology—Cell Physiology, vol. 293, no. 5, pp. C1427–C1436, 2007.
[117]
M. Kodiha, D. Tran, A. Morogan, C. Qian, and U. Stochaj, “Dissecting the signaling events that impact classical nuclear import and target nuclear transport factors,” PloS One, vol. 4, no. 12, article e8420, 2009.
[118]
Z. S. Chughtai, R. Rassadi, N. Matusiewicz, and U. Stochaj, “Starvation promotes nuclear accumulation of the hsp70 Ssa4p in yeast cells,” Journal of Biological Chemistry, vol. 276, no. 23, pp. 20261–20266, 2001.
[119]
X. Quan, P. Tsoulos, A. Kuritzky, R. Zhang, and U. Stochaj, “The carrier Msn5p/Kap142p promotes nuclear export of the hsp70 Ssa4p and relocates in response to stress,” Molecular Microbiology, vol. 62, no. 2, pp. 592–609, 2006.
[120]
X. Quan, R. Rassadi, B. Rabie, N. Matusiewicz, and U. Stochaj, “Regulated nuclear accumulation of the yeast hsp70 Ssa4p in ethanol-stressed cells is mediated by the N-terminal domain, requires the nuclear carrier Nmd5p and protein kinase C,” The FASEB Journal, vol. 18, no. 7, pp. 899–901, 2004.
[121]
A. Chu, N. Matusiewicz, and U. Stochaj, “Heat-induced nuclear accumulation of hsc70s is regulated by phosphorylation and inhibited in confluent cells,” The FASEB Journal, vol. 15, no. 8, pp. 1478–1480, 2001.
[122]
L. Sánchez, M. Kodiha, and U. Stochaj, “Monitoring the disruption of nuclear envelopes in interphase cells with GFP-beta-galactosidase,” Journal of Biomolecular Techniques, vol. 16, no. 3, pp. 235–238, 2005.
[123]
R. S. Faustino, P. Cheung, M. N. Richard et al., “Ceramide regulation of nuclear protein import,” Journal of Lipid Research, vol. 49, no. 3, pp. 654–662, 2008.
[124]
X. Li, K. A. Becker, and Y. Zhang, “Ceramide in redox signaling and cardiovascular diseases,” Cellular Physiology & Biochemistry, vol. 26, no. 1, pp. 41–48, 2010.
[125]
J.-S. Won and I. Singh, “Sphingolipid signaling and redox regulation,” Free Radical Biology & Medicine, vol. 40, no. 11, pp. 1875–1888, 2006.
[126]
R. S. Faustino, L. N. W. Stronger, M. N. Richard et al., “RanGAP-mediated nuclear protein import in vascular smooth muscle cells is augmented by lysophosphatidylcholine,” Molecular Pharmacology, vol. 71, no. 2, pp. 438–445, 2007.
[127]
J. W. Zmijewski, A. Landar, N. Watanabe, D. A. Dickinson, N. Noguchi, and V. M. Darley-Usmar, “Cell signalling by oxidized lipids and the role of reactive oxygen species in the endothelium,” Biochemical Society Transactions, vol. 33, no. 6, pp. 1385–1389, 2005.
[128]
R. S. Faustino, D. C. Rousseau, M. N. Landry, A. L. Kostenuk, and G. N. Pierce, “Effects of mitogen-activated protein kinases on nuclear protein import,” Canadian Journal of Physiology & Pharmacology, vol. 84, no. 3-4, pp. 469–475, 2006.
[129]
R. S. Faustino, T. G. Maddaford, and G. N. Pierce, “Mitogen activated protein kinase at the nuclear pore complex,” Journal of Cellular and Molecular Medicine, vol. 15, no. 4, pp. 928–937, 2011.
[130]
H. Kosako, N. Yamaguchi, C. Aranami et al., “Phosphoproteomics reveals new ERK MAP kinase targets and links ERK to nucleoporin-mediated nuclear transport,” Nature Structural and Molecular Biology, vol. 16, no. 10, pp. 1026–1035, 2009.
[131]
S.-O. Yoon, S. Shin, Y. Liu et al., “Ran-binding protein 3 phosphorylation links the Ras and PI3-kinase pathways to nucleocytoplasmic transport,” Molecular Cell, vol. 29, no. 3, pp. 362–375, 2008.
[132]
F. Dai, X. Lin, C. Chang, and X.-H. Feng, “Nuclear export of Smad2 and Smad3 by RanBP3 facilitates termination of TGF-beta signaling,” Developmental Cell, vol. 16, no. 3, pp. 345–357, 2009.
[133]
K. Koli, M. Myll？rniemi, J. Keski-Oja, and V. L. Kinnula, “Transforming growth factor-β activation in the lung: focus on fibrosis and reactive oxygen species,” Antioxidants & Redox Signaling, vol. 10, no. 2, pp. 333–342, 2008.
[134]
X. Z. Shi, J. H. Winston, and S. K. Sarna, “Differential immune and genetic responses in rat models of Crohn's colitis and ulcerative colitis,” The American Journal of Physiology—Gastrointestinal & Liver Physiology, vol. 300, no. 1, pp. G41–G51, 2011.
[135]
H. Sone, H. Akanuma, and T. Fukuda, “Oxygenomics in environmental stress,” Redox Report, vol. 15, no. 3, pp. 98–114, 2010.
[136]
G. H. Tesch and A. K. Lim, “Recent insights into diabetic renal injury from the db/db mouse model of type 2 diabetic nephropathy,” The American Journal of Physiology—Renal Physiology, vol. 300, no. 2, pp. F301–F310, 2011.
[137]
C. S. Hill, “Nucleocytoplasmic shuttling of Smad proteins,” Cell Research, vol. 19, no. 1, pp. 36–46, 2009.
[138]
M. A. D'Angelo, M. Raices, S. H. Panowski, and M. W. Hetzer, “Age-dependent deterioration of nuclear pore complexes causes a loss of nuclear integrity in postmitotic cells,” Cell, vol. 136, no. 2, pp. 284–295, 2009.
[139]
P. Anderson and N. Kedersha, “Stress granules: the Tao of RNA triage,” Trends in Biochemical Sciences, vol. 33, no. 3, pp. 141–150, 2008.
[140]
M. G. Thomas, M. Loschi, M. A. Desbats, and G. L. Boccaccio, “RNA granules: the good, the bad and the ugly,” Cellular Signalling, vol. 23, no. 2, pp. 324–334, 2011.
[141]
J. R. Buchan and R. Parker, “Eukaryotic stress granules: the ins and outs of translation,” Molecular Cell, vol. 36, no. 6, pp. 932–941, 2009.
[142]
N.-P. Tsai and L.-N. Wei, “RhoA/ROCK1 signaling regulates stress granule formation and apoptosis,” Cellular Signalling, vol. 22, no. 4, pp. 668–675, 2010.
[143]
N.-P. Tsai, P.-C. Ho, and L.-N. Wei, “Regulation of stress granule dynamics by Grb7 and FAK signalling pathway,” The EMBO Journal, vol. 27, no. 5, pp. 715–726, 2008.
[144]
S. Basuroy, M. Dunagan, P. Sheth, A. Seth, and R. K. Rao, “Hydrogen peroxide activates focal adhesion kinase and c-Src by a phosphatidylinositol 3 kinase-dependent mechanism and promotes cell migration in Caco-2 cell monolayers,” The American Journal of Physiology—Gastrointestinal & Liver Physiology, vol. 299, no. 1, pp. G186–G195, 2010.
[145]
K. Fujimura, T. Suzuki, Y. Yasuda, M. Murata, J. Katahira, and Y. Yoneda, “Identification of importin α1 as a novel constituent of RNA stress granules,” Biochimica et Biophysica Acta—Molecular Cell Research, vol. 1803, no. 7, pp. 865–871, 2010.
[146]
S. Mollet, N. Cougot, A. Wilczynska et al., “Translationally repressed mRNA transiently cycles through stress granules during stress,” Molecular Biology of the Cell, vol. 19, no. 10, pp. 4469–4479, 2008.
[147]
W. J. Kim, S. H. Back, V. Kim, I. Ryu, and S. K. Jang, “Sequestration of TRAF2 into stress granules interrupts tumor necrosis factor signaling under stress conditions,” Molecular and Cellular Biology, vol. 25, no. 6, pp. 2450–2462, 2005.
[148]
N. Kedersha and P. Anderson, “Mammalian stress granules and processing bodies,” Methods in Enzymology, vol. 431, pp. 61–81, 2007.
[149]
L. Weinmann, J. H？ck, T. Ivacevic et al., “Importin 8 is a gene silencing factor that targets argonaute proteins to distinct mRNAs,” Cell, vol. 136, no. 3, pp. 496–507, 2009.
[150]
W.-L. Chang and W.-Y. Tarn, “A role for transportin in deposition of TTP to cytoplasmic RNA granules and mRNA decay,” Nucleic Acids Research, vol. 37, no. 19, pp. 6600–6612, 2009.
[151]
M. Ito, K. Miyado, K. Nakagawa et al., “Age-associated changes in the subcellular localization of phosphorylated p38 MAPK in human granulosa cells,” Molecular Human Reproduction, vol. 16, no. 12, pp. 928–937, 2010.
[152]
N. R. Leslie, “The redox regulation of PI 3-kinase-dependent signaling,” Antioxidants & Redox Signaling, vol. 8, no. 9-10, pp. 1765–1774, 2006.
[153]
P. Storz, “Reactive oxygen species-mediated mitochondria-to-nucleus signaling: a key to aging and radical-caused diseases,” Science's STKE, vol. 2006, no. 332, p. re3, 2006.
[154]
J.-F. L. Bodart, “Extracellular-regulated kinase—mitogen-activated protein kinase cascade: unsolved issues,” Journal of Cellular Biochemistry, vol. 109, no. 5, pp. 850–857, 2010.
[155]
L. T. May and S. J. Hill, “ERK phosphorylation: spatial and temporal regulation by G protein-coupled receptors,” The International Journal of Biochemistry & Cell Biology, vol. 40, no. 10, pp. 2013–2017, 2008.
[156]
B. Ananthanarayanan, Q. Ni, and J. Zhang, “Signal propagation from membrane messagers to nuclear effectors revealed by reporters of phosphoinositide dynamics and Akt activity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 42, pp. 15081–15086, 2005.
[157]
A. Kumar, J. Redondo-Mu？oz, V. Perez-García, I. Cortes, M. Chagoyen, and A. C. Carrera, “Nuclear but not cytosolic phosphoinositide 3-kinase beta has an essential function in cell survival,” Molecular and Cellular Biology, vol. 31, no. 10, pp. 2122–2133, 2011.
[158]
M. Kodiha and U. Stochaj, “Targeting AMPK for therapeutic intervention in type 2 diabetes,” in Medical Complications of Type 2 Diabetes, C. Croniger, Ed., InTech, 2011, http://www.intechopen.com/articles/show/title/targeting-ampk-for-therapeutic-intervention-in-type-2-diabetes.
[159]
D. G. Hardie, “AMPK: a key regulator of energy balance in the single cell and the whole organism,” International Journal of Obesity, vol. 32, supplement 4, pp. S7–S12, 2008.
[160]
G. R. Steinberg and B. E. Kemp, “AMPK in health and disease,” Physiological Reviews, vol. 89, no. 3, pp. 1025–1078, 2009.
[161]
B. Viollet, S. Horman, J. Leclerc et al., “AMPK inhibition in health and disease,” Critical Reviews in Biochemistry & Molecular Biology, vol. 45, no. 4, pp. 276–295, 2010.
[162]
N. Kazgan, T. Williams, L. J. Forsberg, and J. E. Brenman, “Identification of a nuclear export signal in the catalytic subunit of AMP-activated protein kinase,” Molecular Biology of the Cell, vol. 21, no. 19, pp. 3433–3442, 2010.
[163]
W. Wang, X. Yang, T. Kawai et al., “AMP-activated protein kinase-regulated phosphorylation and acetylation of importin α1: involvement in the nuclear import of RNA-binding protein HuR,” Journal of Biological Chemistry, vol. 279, no. 46, pp. 48376–48388, 2004.
[164]
H. W. Lo and M. C. Hung, “Nuclear EGFR signalling network in cancers: linking EGFR pathway to cell cycle progression, nitric oxide pathway and patient survival,” The British Journal of Cancer, vol. 94, no. 2, pp. 184–188, 2006.
[165]
Y.-N. Wang, H. Yamaguchi, L. Huo et al., “The translocon Sec61β localized in the inner nuclear membrane transports membrane-embedded EGF receptor to the nucleus,” Journal of Biological Chemistry, vol. 285, no. 49, pp. 38720–38729, 2010.
[166]
H.-W. Lo, M. Ali-Seyed, Y. Wu, G. Bartholomeusz, S. C. Hsu, and M. C. Hung, “Nuclear-cytoplasmic transport of EGFR involves receptor endocytosis, importin β1 and CRM1,” Journal of Cellular Biochemistry, vol. 98, no. 6, pp. 1570–1583, 2006.
[167]
C.-J. Chang, D. J. Mulholland, B. Valamehr, S. Mosessian, W. R. Sellers, and H. Wu, “PTEN nuclear localization is regulated by oxidative stress and mediates p53-dependent tumor suppression,” Molecular and Cellular Biology, vol. 28, no. 10, pp. 3281–3289, 2008.
[168]
J.-L. Liu, Z. Mao, T. A. LaFortune et al., “Cell cycle-dependent nuclear export of phosphatase and tensin homologue tumor suppressor is regulated by the phosphoinositide-3-kinase signaling cascade,” Cancer Research, vol. 67, no. 22, pp. 11054–11063, 2007.
[169]
I. Dalle-Donne, G. Aldini, M. Carini, R. Colombo, R. Rossi, and A. Milzani, “Protein carbonylation, cellular dysfunction, and disease progression,” Journal of Cellular and Molecular Medicine, vol. 10, no. 2, pp. 389–406, 2006.
[170]
P. Wang, G.-H. Liu, K. Wu et al., “Repression of classical nuclear export by S-nitrosylation of CRM1,” Journal of Cell Science, vol. 122, no. 20, pp. 3772–3779, 2009.
[171]
E. Giannoni, M. L. Taddei, and P. Chiarugi, “Src redox regulation: again in the front line,” Free Radical Biology and Medicine, vol. 49, no. 4, pp. 516–527, 2010.
[172]
T. Adachi, D. R. Pimentel, T. Heibeck et al., “S-glutathiolation of Ras mediates redox-sensitive signaling by angiotensin II in vascular smooth muscle cells,” Journal of Biological Chemistry, vol. 279, no. 28, pp. 29857–29862, 2004.
[173]
A. Aghajanian, E. S. Wittchen, S. L. Campbell, and K. Burridge, “Direct activation of RhoA by reactive oxygen species requires a redox-sensitive motif,” PloS One, vol. 4, no. 11, article e8045, 2009.
[174]
N. Brandes, S. Schmitt, and U. Jakob, “Thiol-based redox switches in eukaryotic proteins,” Antioxidants & Redox Signaling, vol. 11, no. 5, pp. 997–1014, 2009.
[175]
E. Giannoni, F. Buricchi, G. Grimaldi et al., “Redox regulation of anoikis: reactive oxygen species as essential mediators of cell survival,” Cell Death & Differentiation, vol. 15, no. 5, pp. 867–878, 2008.
[176]
E. Giannoni, G. Raugei, P. Chiarugi, and G. Ramponi, “A novel redox-based switch: LMW-PTP oxidation enhances Grb2 binding and leads to ERK activation,” Biochemical & Biophysical Research Communications, vol. 348, no. 2, pp. 367–373, 2006.
[177]
C. Butkinaree, K. Park, and G. W. Hart, “O-linked β-N-acetylglucosamine (O-GlcNAc): extensive crosstalk with phosphorylation to regulate signaling and transcription in response to nutrients and stress,” Biochimica et Biophysica Acta—General Subjects, vol. 1800, no. 2, pp. 96–106, 2010.
[178]
R. M. Green, M. Graham, M. R. O'Donovan, J. K. Chipman, and N. J. Hodges, “Subcellular compartmentalization of glutathione: correlations with parameters of oxidative stress related to genotoxicity,” Mutagenesis, vol. 21, no. 6, pp. 383–390, 2006.
[179]
F. Johnson and C. Giulivi, “Superoxide dismutases and their impact upon human health,” Molecular Aspects of Medicine, vol. 26, no. 4-5, pp. 340–352, 2005.
[180]
M. Schrader and H. D. Fahimi, “Peroxisomes and oxidative stress,” Biochimica et Biophysica Acta—Molecular Cell Research, vol. 1763, no. 12, pp. 1755–1766, 2006.
[181]
P. D. Vivancos, Y. Dong, K. Ziegler et al., “Recruitment of glutathione into the nucleus during cell proliferation adjusts whole-cell redox homeostasis in Arabidopsis thaliana and lowers the oxidative defence shield,” The Plant Journal, vol. 64, no. 5, pp. 825–838, 2010.
[182]
J. Markovic, N. J. Mora, A. M. Broseta et al., “The depletion of nuclear glutathione impairs cell proliferation in 3t3 fibroblasts,” PLoS One, vol. 4, no. 7, article e6413, 2009.
[183]
K. Kamada, S. Goto, T. Okunaga et al., “Nuclear glutathione S-transferase π prevents apoptosis by reducing the oxidative stress-induced formation of exocyclic DNA products,” Free Radical Biology & Medicine, vol. 37, no. 11, pp. 1875–1884, 2004.
[184]
J. C. Young, J. M. Barral, and F. U. Hartl, “More than folding: localized functions of cytosolic chaperones,” Trends in Biochemical Sciences, vol. 28, no. 10, pp. 541–547, 2003.
[185]
P. Bański, M. Kodiha, and U. Stochaj, “Chaperones and multitasking proteins in the nucleolus: networking together for survival?” Trends in Biochemical Sciences, vol. 35, no. 7, pp. 361–367, 2010.
[186]
P. Bański, M. Kodiha, and U. Stochaj, “Exploring the nuclear proteome: novel concepts for chaperone trafficking and function,” Current Proteomics, vol. 8, no. 1, pp. 59–82, 2011.
[187]
O. Huet, L. Dupic, A. Harrois, and J. Duranteau, “Oxidative stress and endothelial dysfunction during sepsis,” Frontiers in Bioscience, vol. 16, no. 5, pp. 1986–1995, 2011.
[188]
J. Pi, Q. Zhang, J. Fu et al., “ROS signaling, oxidative stress and Nrf2 in pancreatic beta-cell function,” Toxicology and Applied Pharmacology, vol. 244, no. 1, pp. 77–83, 2010.
[189]
V. Paupe, E. P. Dassa, S. Goncalves et al., “Impaired nuclear Nrf2 translocation undermines the oxidative stress response in Friedreich ataxia,” PLoS One, vol. 4, no. 1, article e4253, 2009.
