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Autophagy protects against senescence and apoptosis via the RAS-mitochondria in high-glucose-induced endothelial cells.

Authors :
Chen F
Chen B
Xiao FQ
Wu YT
Wang RH
Sun ZW
Fu GS
Mou Y
Tao W
Hu XS
Hu SJ
Source :
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology [Cell Physiol Biochem] 2014; Vol. 33 (4), pp. 1058-74. Date of Electronic Publication: 2014 Apr 09.
Publication Year :
2014

Abstract

Backgrounds: Autophagy is an important process in the pathogenesis of diabetes and plays a critical role in maintaining cellular homeostasis. However, the autophagic response and its mechanism in diabetic vascular endothelium remain unclear.<br />Methods and Results: We studied high-glucose-induced renin-angiotensin system (RAS)-mitochondrial damage and its effect on endothelial cells. With regard to therapeutics, we investigated the beneficial effect of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs) against high-glucose-induced endothelial responses. High glucose activated RAS, enhanced mitochondrial damage and increased senescence, apoptosis and autophagic-responses in endothelial cells, and these effects were mimicked by using angiotensin II (Ang). The use of an ACEI or ARB, however, inhibited the negative effects of high glucose. Direct mitochondrial injury caused by carbonyl cyanide 3-chlorophenylhydrazone (CCCP) resulted in similar negative effects of high glucose or Ang and abrogated the protective effects of an ACEI or ARB. Additionally, by impairing autophagy, high-glucose-induced senescence and apoptosis were accelerated and the ACEI- or ARB-mediated beneficial effects were abolished. Furthermore, increases in FragEL™ DNA Fragmentation (TUNEL)-positive cells, β-galactosidase activation and the expression of autophagic biomarkers were revealed in diabetic patients and rats, and the treatment with an ACEI or ARB decreased these responses.<br />Conclusions: These data suggest that autophagy protects against senescence and apoptosis via RAS-mitochondria in high-glucose-induced endothelial cells.<br /> (© 2014 S. Karger AG, Basel.)

Details

Language :
English
ISSN :
1421-9778
Volume :
33
Issue :
4
Database :
MEDLINE
Journal :
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
Publication Type :
Academic Journal
Accession number :
24732710
Full Text :
https://doi.org/10.1159/000358676