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2 PublicationsExtracellular signal-regulated kinase mediates steroidogenesis induced by native and oxidized low-density lipoprotein
Kopprasch, S.; Ansurudeen, I.; Pietzsch, J.; Graessler, J.; Bornstein, S. R.
Abstract
Objectives:
Oxidative stress with resulting oxidation of low-density lipoproteins (LDL) plays a critical role in the atherogenesis. Since hypertension and dyslipidemia are associated with hormonal dysregulation we examined the effect of oxidatively modified LDL on adrenocortical aldosterone and cortisol synthesis.
Methods:
LDL obtained from healthy volunteers by very fast ultracentrifugation was oxidized in vitro by sodium hypochlorite resulting in molar oxidant to LDL ratios of 272:1 (oxLDL-272, minimally oxidized LDL), 543:1 (oxLDL-543, mildly oxidized LDL), and 2716:1 (oxLDL-2716, heavily oxidized LDL). Human NCI-H295R adrenocortical cells were cultured in DMEM/F12. Cell proteins were separated by SDS-PAGE (10%) and immunoblotted with a polyclonal antibody against pERK 1/2 (1:1000). Aldosterone was measured by RIA and cortisol release was determined by competitive luminometric assay.
Results:
Incubation of adrenocortical cells with 10 to 100µg/mL native LDL (natLDL) or oxidized LDL (oxLDL) for 24h stimulated aldosterone release dose-dependently up to 3-fold. Subsequent stimulation of NCI-H295R cells with angiotensin II induced an additional aldosterone secretion up to 2.9-fold in LDL-pretreated samples. Similar effects were observed for cortisol release. Compared to natLDL, oxLDL induced a smaller hormone release. The ability of oxLDL to induce hormone release decreased with increasing degree of LDL oxidation. NatLDL and oxLDL induced ERK phosphorylation with a maximum at 5min poststimulation. Blocking ERK activation with U0126, the inhibitor of ERK upstream kinase MEK, markedly reduced aldosterone release.
Conclusion:
Oxidative modification of LDL decreases adrenocortical aldosterone and cortisol release. The ERK signalling cascade is critically involved in LDL-induced hormone release.
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Poster
51st Annual Meeting of the German Society of Endocrinology (DGE) and 12th Annual Meeting of the Austrian Society of Endocrinology and Metabolism, 07.-10.03.2007, Salzburg, Österreich -
Abstract in refereed journal
Experimental and Clinical Endocrinology & Diabetes 115(2007)Suppl 1, S75
Permalink: https://www.hzdr.de/publications/Publ-10157