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Horm Metab Res 2015; 47(11): 855-860
DOI: 10.1055/s-0034-1395568
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

Crosstalk Between Glycoxidative Modification of Low-Density Lipoprotein, Angiotensin II-Sensitization, and Adrenocortical Aldosterone Release

S. Saha
1   Department of Internal Medicine 3, Carl Gustav Carus Medical School,Technische Universität Dresden, Dresden, Germany
,
S. R. Bornstein
1   Department of Internal Medicine 3, Carl Gustav Carus Medical School,Technische Universität Dresden, Dresden, Germany
,
J. Graessler
1   Department of Internal Medicine 3, Carl Gustav Carus Medical School,Technische Universität Dresden, Dresden, Germany
,
S. Kopprasch
1   Department of Internal Medicine 3, Carl Gustav Carus Medical School,Technische Universität Dresden, Dresden, Germany
› Author Affiliations
Further Information

Publication History

received 23 June 2014

accepted 28 October 2014

Publication Date:
20 January 2015 (online)

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Abstract

Low-density lipoprotein (LDL) is considered to be a risk factor for atherosclerosis. In the presence of hyperglycemia, LDL undergoes glycoxidative modification and this glycoxidized (glycox) LDL promotes atherosclerosis in type 2 diabetic (T2D) individuals. Moreover, because of its cholesterol content, LDL contributes to aldosterone biosynthesis, which is modulated by angiotensin II (AngII) and has been implicated in cardiovascular complications of T2D. However, the molecular mechanism of the crosstalk between glycoxLDL, AngII, and aldosterone has not been explained clearly. Therefore, this study has been aimed to investigate the impact of in vitro modified glycoxLDL on aldosterone release in an AngII-sensitized adrenocortical carcinoma cell line (NCI H295R). Native LDL (natLDL), isolated from healthy volunteers by sequential density gradient ultracentrifugation, was subjected to d-glucose (200 mmol/l), for glycoxidative modification, at 37°C for 6 days. The AngII-sensitized H295R cells were treated with natLDL and glycoxLDL for 24 h and the supernatant was used for aldosterone measurement. The treated cells were utilized for protein isolation and mRNA quantification. Compared to natLDL, glycoxLDL produced a significantly greater effect on aldosterone release from AngII-sensitized cells. The treatment with specific pharmacological inhibitors suggests that modified LDL recruits ERK1/2 and janus kinase-2 for transcriptional regulation of aldosterone synthase. Moreover, glycoxLDL modulates aldosterone release via cAMP-dependent protein kinase A (PKA) pathway. However, glycoxLDL induces ERK phosphorylation independent of PKA activation and this novel mechanism could be targeted for therapeutic trials. In conclusion, this in vitro study emphasizes a possible causal relationship between LDL glycoxidative modification, AngII-sensitization, and adrenocortical steroid hormone release.

Key words

low-density lipoprotein - glycoxidative lipoprotein modification - aldosterone - Janus kinase - protein kinase A
 

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