Chapter 10 - The role of phosphoinositide-specific phospholipase C enzymes in normal, regenerating, and pathological liver

Abstract

The liver acts crucially in different physiological processes, including storage and metabolism of nutrients, synthesis of molecules, and purification of chemicals, thus representing a complex metabolic system. A plethora of factors, including toxic chemicals, viruses, drugs, and alcohol, can disrupt its normal functions leading to different liver illnesses, such as steatosis, hepatitis, fibrosis/cirrhosis, and cancer. Numerous different signal transduction pathways contribute to the organization of the complex activities of the liver. The phosphoinositide (PI) signal transduction pathway was described to participate in liver metabolism, and abnormal activity or expression of PI-specific phospholipase C (PLC) enzymes was described in liver diseases. PLC enzymes are functionally connected to several regulatory molecules, including G protein subunits, small GTPases from Rho and RAS families, receptor and nonreceptor tyrosine kinases, and further lipid components of the cell plasma-membrane. In the liver, selected PLC isoforms interact and are abnormally expressed in a conspicuous number of human liver anomalies, i.e., in the progression of hepatocellular carcinoma (HCC). In human hepatic angiosarcoma, PLC enzymes were demonstrated to contribute resistance to chemotherapy, and PLCs were involved in mouse hepatoma ascites in high metastatic potential cell lines. PLC enzymes were also claimed to play a role in the histopathology features observed in the liver following alcohol abuse. In this review, the involvement of the activity of PLC enzymes in normal, regenerating, and pathological liver will be described.