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

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

Current Trends in Endocrinology

Gateway

Año: 2008 vol. 3 p. 57 - 75

0972-947X

Long-chain fatty acids represent a mayor energy source for many organs. However besides this basal 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 release and it may be metabolized via the ciclooxygenase, lipoxygenase or epoxygenase pathways. How the cells drive AA to these pathways is not fully described. Several reports have shown that AA and its lipoxigenated and epoxigenated products play an essential role in the regulation of steroidogenesis, acting at a point between cAMP-dependent protein phosphorylation and the rate limiting step of the biosynthetic pathway i.e., the metabolism of cholesterol to pregnenolone, which is in turn limited by yhe transport 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 review. However, how different protein hormones regulated 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 steroid biosynthesis 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.