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Constitutive release of a novel free radical scavenger by stellate cells that protects hepatocytes from reperfusion injury
Author(s) -
Gandhi Chandrashekhar R
Publication year - 2010
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.24.1_supplement.38.1
Subject(s) - chemistry , free radical scavenger , superoxide dismutase , superoxide , reactive oxygen species , hepatic stellate cell , sephadex , antioxidant , biochemistry , reperfusion injury , size exclusion chromatography , scavenger , pharmacology , microbiology and biotechnology , biology , ischemia , medicine , enzyme
Reactive oxygen species (ROS) produced by inflammatory cells cause injury to hepatocytes. Adjacently located hepatic stellate cells (HSCs) can influence the survival and functions of hepatocytes. We investigated role of HSCs in superoxide‐induced death of hepatocytes. Medium conditioned by HSCs prevented superoxide‐induced death of hepatocytes. The free radical scavenger released by HSCs (mw greater than 100,000 kDa) is heat (70ºC)‐stable and pH (4.5–8.5)‐resistant. The scavenger was partially purified by alcohol precipitation, acetate (pH 4.5) treatment and elution from DEAE cellulose (DE52) resin with 100–200 mM sodium chloride. The DE52 fraction did not contain superoxide dismutase (SOD), a major antioxidant produced by several cell types. Further separation by sephadex gel filtration yielded 3 distinct protein peaks; while none of the peaks individually protected hepatocytes from superoxide‐induced death, combination of peaks 2 and 3 reestablished the superoxide‐scavenging activity. The protein purified by gel chromatography was also found to protect the rat liver from warm ischemia/reperfusion injury. These results demonstrate for the first time that HSCs might protect hepatocytes from oxidative damage by producing a novel free radical scavenger, further purification of which may lead to the isolation of a powerful antioxidant with clinical application. Supported by an NIH grant (DK 54411).