Journal Article

Modulation of Adrenal Aldosterone Release by Oxidative Modification of Low-Density Lipoprotein

Saha, Sarama, Pietzsch, Jens, Ansurudeen, Ishrath, Graessler, Juergen, Kopprasch, Steffi, Ehrhart-Bornstein, Monika, Bornstein, Stefan R.

2010

Overview

Background Serum aldosterone is a causative factor for various metabolic and cardiovascular disorders. Low-density lipoprotein (LDL) is a major cholesterol source for aldosterone steroidogenesis; however, the effect of oxidative modification of LDL on aldosterone release is not known. We studied the effect of hypochlorite-oxidized LDL (oxLDL) on adrenal aldosterone secretion. Methods LDL (native LDL (natLDL)) was obtained from healthy volunteers and oxidatively modified in vitro. NCI-H295R cells were stimulated with natLDL and oxLDL, and the aldosterone release was quantified by radioimmunoassay. Molecular changes were studied with western blot analysis and quantitative RT-PCR analysis. Results NatLDL and oxLDL caused dose-dependent increase in aldosterone release up to threefold. However, the stimulatory effects of modified LDL on aldosterone secretion decreased with increasing degree of LDL oxidation. 24-h incubations with natLDL, mild- and medium-oxidized LDL sensitized the adrenocortical cells to subsequent angiotensin II (Ang II) stimulations by 2.9-, 2.8-, and 2.5-folds, respectively. Heavily oxidized LDL did not sensitize the cells to Ang II stimulations to a similar extent. At the molecular level, the ERK pathway was activated within a minute by both natLDL and oxLDL; however, oxLDL showed a stronger (2.75-fold at 1 and 15min) and longer (15min) activation of ERK than natLDL (twofold). Conclusions This study demonstrates the following: (i) both natLDL and hypochlorite-oxidized LDL utilize ERK pathway to mediate aldosterone release; (ii) mildly oxidized LDL sensitizes the adrenocortical cells to further stimulations by Ang II similar to natLDL that may have a role in pathological processes; (iii) extensive LDL oxidation counteracts adrenocortical aldosterone release.

• Publisher: Oxford University Press,Nature Publishing Group
• Subject: Adrenal Cortex - drug effects / Adrenal Cortex - metabolism / Adrenal Glands - drug effects / Adrenal Glands - metabolism / Aldosterone - metabolism / aldosterone release / aldosterone synthase / Angiotensin II - pharmacology / Arterial hypertension. Arterial hypotension / Biological and medical sciences / Blood and lymphatic vessels / blood pressure / Blotting, Western / Cardiology. Vascular system / Cell Line / Dose-Response Relationship, Drug / ERK / Extracellular Signal-Regulated MAP Kinases - metabolism / Glomerulonephritis / H295R cells / Humans / hypertension / Hypochlorous Acid - chemistry / LDL / Lipoproteins, LDL - chemistry / Lipoproteins, LDL - pharmacology / Medical sciences / Nephrology. Urinary tract diseases / Nephropathies. Renovascular diseases. Renal failure / Oxidants - chemistry / oxidized LDL / Receptors, LDL - drug effects / Receptors, LDL - metabolism / Reverse Transcriptase Polymerase Chain Reaction / RNA - biosynthesis / RNA - isolation & purification / sensitivity to angiotensin II / Steroids - biosynthesis / Stimulation, Chemical / Thiobarbituric Acid Reactive Substances - metabolism