Osmosensing and Osmosignaling in the Liver

Alterations of hepatocyte volume induced by either anisoosmotic environments or under the influence of hormones, concentrative amino acid uptake and oxidative stress are now recognized as an independent signal which contributes to the regulation of liver cell function and gene expression. Several long-known but mechanistically poorly understood effects of amino acids, which could not be related to their metabolism, such as the stimulation of glycogen synthesis or the inhibition of proteolysis are due to their effects on hepatocyte hydration, because they are quantitatively mimicked by swelling the cells in hypoosmotic media to the extent as the amino acids do. Likewise, transmembrane ion movements under the influence of hormones are an integral part of hormonal signal transduction mechanisms with alterations of cellular hydration acting as another "second messenger" of hormone action. Integrins act as osmosensors for hepatocyte swelling and trigger activation of mitogen- activated protein kinase systems as osmosignaling cascades towards choleresis and autophagy inhibition. On the contrary, hepatocyte shrinkage triggers endosomal acidification as a signal for a ceramide-dependent activation of NADPH oxidase isoenzymes, which results in an oxidative stress signal with proapoptotic effects. Disturbances of osmosignaling and osmosensing are involved in a variety of pathophysiological conditions such as insulin resistance, protein catabolic states and cholestatic liver injury. This article briefly summarizes some aspects of our own work on osmosignaling and osmosensing; for indepth surveys the reader is refered to recent reviews [1-6].