Carbon monoxide, a natural product of HO enzymatic action, rescues mice from fulminant hepatitis

Heme oxygenase (HO) enzymes cleave the pro-oxidant heme molecule into carbon monoxide (CO), ferrous iron, and biliverdin, which is subsequently converted to bilirubin. Among three identified isoforms of HO, HO-1 is inducible and widely expressed under stress conditions in parenchymal and non-parenchymal cells of liver. In this study, we showed that HO-1 was protective against fulminant hepatitis in a siRNA experiment. HO-1 suppressed TNFa-induced primary hepatocyte apoptosis mediated by one of its catalytic products, CO. HO-1/CO up-regulated Bcl-xL expression through the activation the p38 MAPK and AKT pathways…