Role of nitric oxide in liver injury.
The complex role of nitric oxide (NO) in the liver can be explained by its patterns of regulation and unique biochemical properties. With a broad range of direct and indirect molecular targets, NO acts as an inhibitor or agonist of cell signaling events. In the liver, constitutively generated NO maintains the hepatic microcirculation and endothelial integrity, while inducible NO synthase (iNOS)-governed NO production can be either beneficial or detrimental. For instance, NO potentiates the hepatic oxidative injury in warm ischemia/reperfusion, while iNOS expression protects against hepatic apoptotic cell death seen in models of sepsis and hepatitis. Anti-apoptotic actions are either cyclic nucleotide dependent or independent, including the expression of heat shock proteins, prevention of mitochondrial dysfunction, and inhibition of caspase activity by S-nitrosation. Whether NO protects or injures is probably determined by the type of insult, the abundance of reactive oxygen species (ROS), the source and amount of NO production and the cellular redox status of liver. Through the use of pharmacological NO donors or NOS gene transfer in conjunction with genetically altered knockout animals, the physiological and pathophysiological roles of NO in liver function can be explored in more detail. The purpose of this paper is to review the current understanding of the role of NO in liver injury.
Chen
Tracy
T
Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Zamora
Ruben
R
Zuckerbraun
Brian
B
Billiar
Timothy R
TR
D000082:Acetaminophen / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury; D022781:Hepatocytes / Q000201:enzymology; D006801:Humans; D008099:Liver / Q000293:injuries* / Q000503:physiopathology; D008107:Liver Diseases / Q000201:enzymology / Q000503:physiopathology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011401:Promoter Regions, Genetic
D009569:Nitric Oxide; D000082:Acetaminophen; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II