Nitric oxide in liver diseases

• eNOS-derived NO is protective against liver diseases, whereas iNOS-derived NO is deleterious.
• In liver biology, eNOS and iNOS are major players, whereas the role of nNOS is little known.
• NO regulates a wide range of cellular activities by binding to metal ions, proteins, lipids, and guanine nucleotides.
• In liver biology, NO signaling through protein modifications by S-guanylation or NO2-FA S-alkylation should be explored.

Nitric oxide (NO) and its derivatives play important roles in the physiology and pathophysiology of the liver. Despite its diverse and complicated roles, certain patterns of the effect of NO on the pathogenesis and progression of liver diseases are observed. In general, NO derived from endothelial NO synthase (eNOS) in liver sinusoidal endothelial cells (LSECs) is protective against disease development, while inducible NOS (iNOS)-derived NO contributes to pathological processes. This review addresses the roles of NO in the development of various liver diseases with a focus on recently published articles. We present here two recent advances in understanding NO-mediated signaling – nitrated fatty acids (NO2-FAs) and S-guanylation – and conclude with suggestions for future directions in NO-related studies on the liver.