Degradation of oxidized or oxidatively modified proteins is an essential
part of the cellular antioxidant defense system. 4-Hydroxy-2-nonenal (HNE), a
major reactive aldehyde formed by lipid peroxidation, causes many types of
cellular damage. HNE-modified proteins are degraded by the ubiquitin-proteasome
pathway or the lysosomal pathway. However, our previous studies using U937
cells showed that HNE-modified glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
is degraded by cathepsin G. In the present study, we examined whether GAPDH
in U937 cells treated with HNE in culture is degraded similarly to that
incubated with HNE and U937 cell extract. Treatment with HNE for 10 min in
culture decreased GAPDH activity in a concentration dependent manner, but did
not affect GAPDH degradation. The proteasome activities were not affected by
HNE, but culturing with HNE decreased cathepsin G activity and protein level in
a concentration dependent manner. These results suggest that HNE-induced
oxidative stress leads to decreased cathepsin G activity and results in the
loss of GAPDH degradation. Taken together, our findings indicate that cathepsin
G has an important role in the degradation of oxidatively modified GAPDH in
U937 cells.
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