Mechanisms of signal transduction in the stress response of hepatocytes

Adaptation of animals to stress is a unique property of life which allows the survival of the species. The stress response of hepatocytes is a very complex phenomenon, sometimes involving a cascade of events. The general stress signals are elucidated by mobilization of carbohydrate stores and akin to the insulin mediators. Oxidative signals are generated by pesticides, heavy metals, drugs, and alcohol which may or may not be under the purview of peroxisomes. Peroxisomal responses are well-defined involving specific receptors, whereas nonperoxisomal responses may be signaled by calcium, the Ah receptor, or built-in antioxidant systems. The intoxication signals are generally thought to be membrane defects induced by xenobiotics which then lead to highly nonspecific responses of hepatocytes. Detoxication signals, on the other hand, are specific responses of hepatocytes triggering de novo syntheses of detoxifier proteins or enzymes. Evidence reveals the existence of two distinct mechanisms of signal transduction in stressed hepatocytes--one involving the peroxisome and the other the plasma membrane.