Chapter 12 - Signaling and transduction mechanism of phospholipase C and isoforms in different cell types

Abstract

The physiological and clinical relevance of the phospholipases enzyme family has been extensively researched. Phospholipases catalyze the hydrolysis of phospholipids, which results in the generation of secondary messengers that play an important part in signal transmission. Phospholipases are divided into different groups, based on their expression and physiologic functions; these include cardiolipin biosynthesis regulation, cardioprotection during oxidative stress, and cognitive development. Phospholipase C (PLC) isoforms are involved in tissue-specific signaling and are triggered by a variety of signaling receptors, including G-protein coupled receptors and tyrosine kinase receptors. The PLC isoform plays a key role in the phosphatidylinositol pathway, in which G-protein activates PLC, which catalyzes the conversion of PIP2 to IP3 and 1, 2-DAG. IP3 and DAG are secondary messengers that are involved in the regulation of cytosolic Ca++ ions and activation of protein kinase (PKC), respectively, which regulate the glycogen metabolism. On the other hand, PLC activated via tyrosine kinase receptor modulates the signal transduction in immune cells by promoting the transcription of genes required for immune response. Furthermore, PLC-γ-1 is abundant in the brain, and plays a role in regulating neurite outgrowth, neuronal cell migration, and postsynaptic signal transduction via PI3/DAG signaling cascade. In vitro and in vivo studies conducted on transgenic mouse showed that PKC activation directs the production of neuroprotective substances and inhibits the production and accumulation of neurotoxic amyloid proteins in AD. Furthermore, PKC is categorized as one of the cognitive kinases controlling memory and learning. Nevertheless, the role of PLC isoform in cognitive development and mechanism is still unclear. In this chapter, we focus on the pathophysiology of neurodegenerative disorders, metabolic dysfunction, and inflammatory diseases by dissecting out the tissue-specific signal transduction by PLC isoform.