Publication:


abstract

Diabetic dyslipidemia is characterized by increased circulatory Very-low-density lipoprotein (VLDL) levels. aldosterone, apart from its role in fluid and electrolyte homeostasis, has also been implicated in insulin resistance and myocardial fibrosis. The impact of VLDL as a potential risk factor for aldosterone-mediated cardiovascular injury in diabetes mellitus, however, remains to be investigated. We have therefore studied native and modified VLDL-mediated steroidogenesis and its underlying molecular mechanisms in human adrenocortical carcinoma cells, NCI H295R. Native VLDL (natVLDL), isolated from healthy volunteers, was subjected to in vitro modification with glucose (200 mmol/l) or sodium hypochlorite (1.5 mmol/l) for preparation of glycoxidized and oxidized VLDL, respectively. VLDL treatment induced steroidogenesis in both a concentration- and time-dependent manner. Native and glycoxidized VLDL (50 μg/ml) were almost two-fold more potent in adrenocortical aldosterone release than angiotensin II (100 nmol/l). These forms of VLDL significantly augmented transcriptional regulation of aldosterone synthase (Cyp11B2), partially through scavenger receptor class B type I, as evident from the effect of BLT-1. In contrast to glycoxidized VLDL, oxidized VLDL significantly attenuated the stimulatory effect of natVLDL on adrenocortical hormone synthesis. Moreover, treatment with specific pharmacological inhibitors (H89, U0126, AG490) provided supporting evidence that VLDL, irrespective of modification, presumably recruited PKA, ERK1/2 and Jak-2 for steroid hormone release through modulation of Cyp11B2 mRNA level. In conclusion, this study demonstrates a novel insight into intracellular mechanism of VLDL-mediated aldosterone synthesis through transcriptional regulation of steroidogenic acute regulatory protein (StAR) and Cyp11B2 expression in human adrenocortical carcinoma cell line.

Related Articles
Diabetic lipoproteins and adrenal aldosterone synthesis--a possible pathophysiological link?
Horm Metab Res. 2012
Diabetic lipoproteins and adrenal aldosterone synthesis--a possible pathophysiological link?
Saha S, Willenberg HS, Bornstein SR, Graessler J, Kopprasch S. Horm Metab Res. 2012 Mar; 44(3):239-44. Epub 2011 Dec 6.
Adrenal cell aldosterone production is stimulated by very-low-density lipoprotein (VLDL).
Endocrinology. 2012
Adrenal cell aldosterone production is stimulated by very-low-density lipoprotein (VLDL).
Xing Y, Rainey WE, Apolzan JW, Francone OL, Harris RB, Bollag WB. Endocrinology. 2012 Feb; 153(2):721-31. Epub 2011 Dec 20.
Human adipocytes induce an ERK1/2 MAP kinases-mediated upregulation of steroidogenic acute regulatory protein (StAR) and an angiotensin II-sensitization in human adrenocortical cells.
Int J Obes (Lond). 2007
Human adipocytes induce an ERK1/2 MAP kinases-mediated upregulation of steroidogenic acute regulatory protein (StAR) and an angiotensin II-sensitization in human adrenocortical cells.
Krug AW, Vleugels K, Schinner S, Lamounier-Zepter V, Ziegler CG, Bornstein SR, Ehrhart-Bornstein M. Int J Obes (Lond). 2007 Oct; 31(10):1605-16. Epub 2007 Apr 24.
Modified high-density lipoprotein modulates aldosterone release through scavenger receptors via extra cellular signal-regulated kinase and Janus kinase-dependent pathways.
Mol Cell Biochem. 2012
Modified high-density lipoprotein modulates aldosterone release through scavenger receptors via extra cellular signal-regulated kinase and Janus kinase-dependent pathways.
Saha S, Graessler J, Schwarz PE, Goettsch C, Bornstein SR, Kopprasch S. Mol Cell Biochem. 2012 Mar 1; . Epub 2012 Mar 1.
Regulation of the scavenger receptor BI and the LDL receptor by activators of aldosterone production, angiotensin II and PMA, in the human NCI-H295R adrenocortical cell line.
Biochim Biophys Acta. 2003
Regulation of the scavenger receptor BI and the LDL receptor by activators of aldosterone production, angiotensin II and PMA, in the human NCI-H295R adrenocortical cell line.
Pilon A, Martin G, Bultel-Brienne S, Junquero D, Delhon A, Fruchart JC, Staels B, Clavey V. Biochim Biophys Acta. 2003 Apr 8; 1631(3):218-28.