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Autophagy protects against senescence and apoptosis via the RAS-mitochondria in high-glucose-induced endothelial cells.
- 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.)
- Subjects :
- Angiotensin II pharmacology
Angiotensin II Type 1 Receptor Blockers pharmacology
Angiotensin-Converting Enzyme Inhibitors pharmacology
Animals
Cellular Senescence drug effects
DNA Fragmentation drug effects
Endothelial Cells cytology
Endothelial Cells drug effects
Endothelial Cells metabolism
Human Umbilical Vein Endothelial Cells
Humans
Hydrazones pharmacology
Membrane Potential, Mitochondrial drug effects
Mitochondria metabolism
Rats
Rats, Sprague-Dawley
Receptor, Angiotensin, Type 1 metabolism
beta-Galactosidase metabolism
Apoptosis drug effects
Autophagy
Glucose pharmacology
Mitochondria drug effects
Renin-Angiotensin System drug effects
Subjects
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