Zinc inhibits ethanol-induced HepG2 cell apoptosis.
Alcohol consumption produces a variety of metabolic alterations in liver cells, associated with ethanol oxidation and with nonoxidative metabolism of ethanol, among others apoptosis of hepatocytes. As zinc is known as a potent antioxidant and an inhibitor of cell apoptosis, the aim of this paper was to investigate whether zinc supplementation could inhibit ethanol-induced HepG2 apoptosis, and whether this inhibition was connected with attenuation of oxidative stress and modulation of FasR/FasL system expression. The results indicated that zinc supplementation significantly inhibited ethanol-induced HepG2 cell apoptosis (measured by cytochrome c release from mitochondria and caspase-3 activation) by attenuation of reactive oxygen species (ROS) production, increase in the cellular level of GSH, inhibition of ethanol-induced sFasR and FasL overexpression and caspase-8 activation. These results indicate that zinc can inhibit ethanol-induced hepatocyte apoptosis by several independent mechanisms, among others by an indirect antioxidative effect and probably by inhibition of caspase-8 and caspase-9 activation.
Szuster-Ciesielska
Agnieszka
A
Department of Virology and Immunology, Maria Curie-Skłodowska University, Akademicka 19, Lublin, Poland. szustera@hektor.umcs.lublin.pl
Plewka
Krzysztof
K
Daniluk
Jadwiga
J
Kandefer-Szerszeń
Martyna
M
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D053181:Caspase 8 / Q000187:drug effects / Q000378:metabolism; D053453:Caspase 9 / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D002492:Central Nervous System Depressants / Q000633:toxicity*; D002712:Chlorides / Q000494:pharmacology*; D045304:Cytochromes c / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D053222:Fas Ligand Protein / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D017967:Zinc Compounds / Q000494:pharmacology*; D019014:fas Receptor / Q000187:drug effects / Q000378:metabolism
D000975:Antioxidants; D002492:Central Nervous System Depressants; D002712:Chlorides; D053222:Fas Ligand Protein; D017382:Reactive Oxygen Species; D017967:Zinc Compounds; D019014:fas Receptor; D000431:Ethanol; C016837:zinc chloride; D045304:Cytochromes c; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D005978:Glutathione