Increasing evidence implicates free radical processes in the pathogenesis of ethanol-induced liver injury. One of the antioxidant defense systems in mammalian cells is the mitochondrial enzyme manganese superoxide dismutase (MnSOD). MnSOD activity is increased by agents that cause oxidative stress. One such agent is the cytokine tumor necrosis factor-α (TNF). Increased serum/tissue TNF levels have been observed in alcoholic liver disease, and TNF has been postulated to play a role in ethanol-induced liver injury. Substantial evidence suggests that ethanol itself can cause oxidative stress. In order to investigate the mechanism of the cellular adaptive response to ethanol-induced oxidative stress, the effects of short-term ethanol exposure on MnSOD RNA, protein, and activity were determined in a human hepatoma cell line (HepG2). We found that exposure to ethanol (25 mMconcentration) for 72 h increased the protein level and enzyme activity of MnSOD. However, examination of the mRNA levels of the enzyme showed no corresponding increase. Long-term administration of ethanol (10 weeks) did not significantly increase MnSOD protein and MnSOD activity. MnSOD activity was significantly increased by TNF. Thus it appears that both TNF and ethanol are capable of increasing MnSOD activity presumably via enhanced oxidative stress. However, unlike TNF, acute ethanol administration increases the activity of MnSOD without increasing MnSOD mRNA. The increase in MnSOD after a short-term dose of ethanol is diminished with repeated ethanol administrations. These findings are compatible with the view that chronic exposure to ethanol suppresses the cellular adaptive response to oxidative stress. If this adaptive response of MnSOD is lessened, it may have implica tions in the increased toxicity due to prolonged ethanol exposure.
|Number of pages||6|
|Journal||Archives of Biochemistry and Biophysics|
|State||Published - Nov 10 1995|
Bibliographical noteFunding Information:
This study was supported by NIH Grants CA-49797, CA-59835, and 3MO1260207S1, CRC MO1RR02602-07, KTRB 5-41113, and the Veterans Administration.
ASJC Scopus subject areas
- Molecular Biology