iNOS Regulation
Our focus for many years concerns the regulation and function
of iNOS in the liver. The enzyme is readily upregulated in hepatocytes,
as our laboratory first showed in 1989. Moreover, human iNOS was
first detected in and cloned from hepatocytes. In vivo studies
have shown that the consequences of iNOS upregulation in liver
are dependent upon the specific physiological or pathological
circumstances. Following conditions associated with severe redox
stress, iNOS contributes to hepatocellular damage as seen in hemorrhagic
shock or hepatic ischemia/reperfusion. In other settings, induced
NO is anti-apoptotic in the liver. Factors that govern the consequences
of iNOS in the liver are poorly understood, but clearly cells
such as HC need mechanisms to regulate iNOS activity in order
to maximize the protective actions while limiting toxicity.
