Alternative Renin Transcripts and Functions of Cytoplasmatic Renin

Abstract

Renin is commonly known as a secretory glycoprotein which is expressed, stored, and secreted in a regulated manner by the kidney. Recently additional renin transcripts have been identified lacking exon 1 and thus the coding sequence for a cotranslational transport to the endoplasmatic reticulum. From these transcripts a non-secretory cytoplasmatic renin is translated. In the rat heart, exclusively cytoplasmatic renin is expressed. Here the expression of cytosolic renin transcripts increases markedly after myocardial infarction, indicating a role for cytosolic renin during and after ischemia. In H9c2-cardiomyoblasts cytosolic renin is targeted at mitochondria, where it stimulates the rate of apoptosis but decreases rate of necrosis. In contrast secretory renin increased the rate of necrosis. In the adrenal gland both secretory and cytosolic renin are expressed. Whereas secretory renin may be part of a secretory intra-adrenal angiotensin amplification system, cytosolic renin is targeted to mitochondria, where it may stimulate aldosterone production by as yet unknown intracellular pathway. In support of this, increased expression of cytosolic renin is associated with increased aldosterone production in transgenic rats.