Evidence for a Mitochondrial Angiotensin-(1-7) System in the Kidney.

Evidence for a Mitochondrial Angiotensin-(1-7) System in the Kidney. Am J Physiol Renal Physiol. 2015 Dec 23;:ajprenal.00479.2015 Authors: Wilson BA, Nautiyal M, Gwathmey TM, Rose JC, Chappell MC Abstract Evidence for an intracellular renin-angiotensin system (RAS) in various cell organelles now includes the endoplasmic reticulum, nucleus and mitochondria (Mito). Indeed, angiotensin (Ang) AT1 and AT2 receptor subtypes were functionally linked to Mito respiration and nitric oxide production, respectively in previous studies. We undertook a biochemical analysis of the Mito RAS from male and female sheep kidney cortex. Mito -were isolated by differential centrifugation followed by a discontinuous Percoll gradient and were co-enriched in Mito membrane markers VDAC and ATP synthase, but not β-actin or cathepsin B. Two distinct renin antibodies identified a 37 kDa protein band in Mito; angiotensinogen (Aogen) conversion was abolished by the inhibitor aliskerin. Mito Aogen was detected by an Aogen antibody to an internal sequence of the protein, but not with an antibody directed against the Ang I N-terminus. Angiotensin peptides were quantified by three direct RIAs; mitochondrial Ang II and Ang-(1-7) contents were higher compared to Ang I [23 ± 8 and 58 ± 17 vs. 2 ± 1 fmol/mg protein; p<0.01, n=3]. (125)I-Ang I metabolism primarily revealed the formation of (125)I-Ang-(1-7) in Mito that reflects the endopeptidases neprilysin and thim...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research