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RETINOIDS PREVENT SUPEROXIDE‐INDUCED APOPTOSIS OF RAT HEPATIC STELLATE CELLS
Author(s) -
Thirunavukkarasu Chinnasamy,
Jameel NM,
Wu Tong,
Gandhi Chandrashekhar R
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a189-b
Subject(s) - glutathione peroxidase , glutathione , reactive oxygen species , retinoic acid , catalase , superoxide dismutase , hepatic stellate cell , oxidative stress , apoptosis , antioxidant , chemistry , dna damage , retinoid , superoxide , biochemistry , medicine , endocrinology , biology , enzyme , dna , gene
Reactive oxygen species stimulate transformation of quiescent retinoid‐containing hepatic stellate cells (qHSCs) into retinoid‐deficient proliferating and fibrogenic activated phenotype (aHSCs). We observed that superoxide (SO) can also cause apoptosis of rat aHSCs. This study investigated mechanisms of the effects of SO on the two HSC phenotypes. Unstimulated qHSCs exhibited spontaneous caspase‐3 activity, DNA damage and apoptosis, which were not affected by SO. In contrast, SO caused DNA damage and apoptosis in aHSCs. The basal glutathione (GSH) and activities of SOD, catalase and glutathione peroxidase (GPx) were significantly lower in aHSCs than qHSCs. SO treatment increased GSH content, and activities of SOD, catalase and GPx in qHSCs but not in aHSCs. Incubation of aHSCs with retinoic acid increased GSH content and GPx activity, but did not alter the activities of SOD and catalase. SO treatment of retinoic acid‐treated aHSCs caused further increase in GSH content and GPx activity, and inhibited its death‐inducing effects. Finally, oxidative stress induced by tertbutylhydroperoxide caused apoptosis of aHSCs in CCl 4 ‐induced cirrhotic rat but not of qHSCs in control rats. Thus absence of retinoids, and lower GSH and activities of antioxidant enzymes seem to render aHSCs susceptible to the damaging effects of SO, which may have important implications in liver pathophysiology.