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Leptin Reduces hypoxia‐reoxygenation‐induced Fas/FasL gene overexpression and apoptosis in human L02 cells
Author(s) -
Zhou Shaoli,
Chen Guihua,
Li Xiaoyun,
Li Shangrong,
Guo Na,
Irwin Michael G,
Xia Zhengyuan,
Hei Ziqing
Publication year - 2012
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.26.1_supplement.798.5
Subject(s) - fas ligand , leptin , apoptosis , hypoxia (environmental) , endocrinology , medicine , reperfusion injury , hepatocyte , chemistry , biology , programmed cell death , ischemia , biochemistry , organic chemistry , oxygen , in vitro , obesity
Fas/FasL activation induces caspase‐3 activation that may exacerbate hepatic ischemia‐reperfusion injury (IRI) by increasing apoptotic cell death. Leptin, an endogenous cytokine, facilitates cell growth and attenuates hypoxic brain injury (Stroke, 2007;8:2329–2336). We postulated that leptin may attenuate hypoxia/reoxygenation‐induced hepatocyte injury by reducing apoptosis and suppressing Fas/FasL gene expression. Human hepatic L02 cell IRI was induced by exposing the cell to hypoxia for 12 hours followed by 12 hours reoxygenation in the absence or presence of different concentrations of leptin (100 μg/L, 200 μg/L, 400 μg/L, 800 μg/L and 1600 μg/L). Cell survival rates were significantly reduced in cells subjected to IRI compared to control cells receiving normoxia accompanied with increased apoptotic index as measured by flow cytometry and terminal dUTP nick‐end labeling, which was coincident with increased gene expressions of Fas and FasL (all P<0.01, group IRI vs. control). All the above changes were significantly attenuated by treatments with various concentrations of leptin (all P<0.05, vs. group IRI), while the optimal effects were seen at leptin concentration of 400 μg/L. It is concluded that leptin may have reduced hypoxia/reoxygenation‐induced hepatic L02 cell apoptosis by down‐regulating Fas/FasL gene expression. Supported by a Doctoral Start‐up Foundation grant in (NO. 10451008901004797)