Mitochondrial aldehyde dehydrogenase 2 protects against high glucose-induced injury in neonatal rat cardiomyocytes by regulating CaN-NFAT3 signaling pathway.
10.12122/j.issn.1673-4254.2018.11.02
- Author:
Jianlu GUO
1
;
Pinfang KANG
1
;
Lei ZHU
1
;
Shuo SUN
1
;
Min TAO
2
;
Heng ZHANG
1
;
Bi TANG
1
Author Information
1. Department of Cardiology, First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China.
2. Department of Cardiology, Huishan District People's Hospital, Wuxi 214100, China.
- Publication Type:Journal Article
- Keywords:
activated T cell nuclear factor 3;
calcineurin;
high glucose;
mitochondrial acetaldehyde dehydrogenase 2
- MeSH:
Aldehyde Dehydrogenase, Mitochondrial;
antagonists & inhibitors;
metabolism;
Animals;
Animals, Newborn;
Benzamides;
pharmacology;
Benzodioxoles;
pharmacology;
Calcium;
metabolism;
Cells, Cultured;
Culture Media;
Enzyme Inhibitors;
pharmacology;
Glucose;
administration & dosage;
pharmacology;
Isoflavones;
pharmacology;
Mitochondria, Heart;
enzymology;
Myocytes, Cardiac;
drug effects;
metabolism;
NFATC Transcription Factors;
metabolism;
Nuclear Pore Complex Proteins;
metabolism;
Rats;
Rats, Sprague-Dawley
- From:
Journal of Southern Medical University
2018;38(11):1288-1293
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate whether CaN-NFAT3 pathway mediates the protective effects of aldehyde dehydrogenase (ALDH) 2 in high glucose-treated neonatal rat ventricular myocytes.
METHODS:The ventricular myocytes were isolated from the heart of neonatal (within 3 days) SD rats by enzyme digestion and cultured in the presence of 5-Brdu. After reaching confluence, the cultured ventricular myocytes were identified using immunofluorescence assay for -SA protein. The cells were then cultured in either normal (5 mmol/L) or high glucose (30 mmol/L) medium in the presence of ALDH2 agonist Alda-1, ALDH 2 inhibitor Daidzin, or Alda-1 and NFAT3 inhibitor (11R-VIVIT). Fluorescent probe and ELISA were used to detect intracellular Ca concentration and CaN content, respectively; ALDH2, CaN and NFAT3 protein expressions in the cells were detected using Western blotting.
RESULTS:Compared with cells cultured in normal glucose, the cells exposed to high glucose showed a significantly decreased expression of ALDH2 protein ( < 0.05) and increased expressions of CaN ( < 0.05) and NFAT3 proteins with also increased intracellular CaN and Ca concentrations ( < 0.01). Alda-1 treatment significantly lowered Ca concentration ( < 0.05), intracellular CaN content ( < 0.01), and CaN and NFAT3 protein expressions ( < 0.05), and increased ALDH2 protein expression ( < 0.05) in high glucose- exposed cells; Daidzin treatment significantly increased Ca concentration ( < 0.01) and intracellular CaN content ( < 0.05) in the exposed cells. Compared with Alda-1 alone, treatment of the high glucose-exposed cells with both Alda-1 and 11R-VIVIT did not produce significant changes in the expression of ALDH2 protein (>0.05) but significantly reduced the expression of NFAT3 protein ( < 0.05).
CONCLUSIONS:Mitochondrial ALDH2 protects neonatal rat cardiomyocytes against high glucose-induced injury possibly by negatively regulating Ca-CaN-NFAT3 signaling pathway.
