Review: Intramitochondrial arachidonic acid as regulator of two different cellular functions: steroid biosynthesis and tumor cell proliferation.

CASTILLO ANA FERNANDA; CASTILLA ROCÍO; DUARTE ALEJANDRA; MELE PABLO; ORLANDO ULISES; KARLES CRISTINA; NEUMAN ISABEL; DI CONSOLI HERNAN; PODEROSO CECILIA; SOLANO ANGELA; FINKIELSTEIN CARLA; MALOBERTI PAULA; CORNEJO MACIEL FABIANA; PAZ CRISTINA; PODESTA ERNESTO JORGE

Current trends in endocrinology

Gateway

Año: 2008 vol. 3 p. 57 - 75

0972-947X

Long-chain fatty acids represent a major energy source for many organs. However besides thisbasal function, long-chain-acyl-CoA esters also have an important function in cell signaling. Arachidonic acid (AA) is a 20-carbon fatty acid and it is a common constituent of phospholipids in cell membranes. On stimulation of a cell, free AA is released and it may be metabolized viathe cyclooxygenase, lipoxygenase or epoxygenase pathways. How the cells drive AA to thesepathways is not fully described. Several reports have shown that AA and its lipoxygenated andepoxygenated products play an essential role in the regulation of steroidogenesis, acting at a pointbetween cAMP-dependent protein phosphorylation and the rate limiting step of the biosyntheticpathway -i.e., the metabolism of cholesterol to pregnenolone, which is in turn limited by thetransport of cholesterol from the outer to the inner mitochondrial membrane. Cholesterol transfer is controlled by a multiple protein complex including the translocator protein and the steroidogenic acute regulatory protein (StAR). This topic has been well covered in specialized reviews. However, how different protein hormones regulate this universal process in steroid biosynthesis throughout different signal transduction mechanisms in different tissues is still not cover by any review. AA is one of the common intermediates in the regulation of steroidbiosynthesis by different factors. This review covers the mechanism by which steroidogenic hormones control AA release and metabolization to lipoxygenated and epoxygenated metabolites to induce StAR protein and steroidogenesis and how AA is related also to proliferation and carcinogenesis.