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Aldehyde dehydrogenase-2 (ALDH2) ameliorates chronic alcohol ingestion-induced myocardial insulin resistance and endoplasmic reticulum stress.
J Mol Cell Cardiol. 2009 Aug; 47(2):247-55.JM

Abstract

Chronic alcohol intake leads to insulin resistance and alcoholic cardiomyopathy, which appears to be a result of the complex interaction between genes and environment. This study was designed to examine the impact of aldehyde dehydrogenase-2 (ALDH2) transgenic overexpression on alcohol-induced insulin resistance and myocardial injury. ALDH2 transgenic mice were produced using chicken beta-actin promoter. Wild-type FVB and ALDH2 mice were fed a 4% alcohol or control diet for 12 weeks. Cell shortening was evaluated using an edge-detection system. Western blot analysis was used to assess insulin signaling at the levels of receptor, IRS, Akt, GSK-3beta, the transcription factors Foxo3a, c-Jun amino-terminal kinase (JNK) and c-Jun. Chronic alcohol intake led to glucose intolerance, reduced glucose uptake, cardiac hypertrophy and reduced cell shortening, the effects of which were alleviated by ALDH2. ALDH2 significantly attenuated alcohol-induced decrease in the insulin-stimulated tyrosine phosphorylation and increase in serine phosphorylation of IRS. Phosphorylation of Akt, GSK-3beta and Foxo3a was reduced following alcohol intake, the effect of which was abrogated by ALDH2. Levels of JNK, c-Jun and their phosphorylation were elevated following chronic alcohol intake, which were obliterated by ALDH2. Transfection of H9C2 myoblast cells with Foxo3a adenovirus mimicked acetaldehyde-induced JNK activation and glucose uptake defect whereas the dominant negative Foxo3a ablated acetaldehyde-elicited insulin insensitivity. In addition, ALDH2 reversed alcohol-induced myocardial ER stress. These data revealed that ALDH2 overexpression antagonizes chronic alcohol intake-induced cardiac insulin insensitivity and contractile defect, possibly via improvement of insulin signaling at the levels of insulin receptor, IRS, Akt, Foxo3a and JNK.

Authors+Show Affiliations

Center for Cardiovascular Research and Alternative Medicine, School of Pharmacy, University of Wyoming College of Health Sciences, Laramie, WY 82071, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19344727

Citation

Li, Shi-Yan, et al. "Aldehyde Dehydrogenase-2 (ALDH2) Ameliorates Chronic Alcohol Ingestion-induced Myocardial Insulin Resistance and Endoplasmic Reticulum Stress." Journal of Molecular and Cellular Cardiology, vol. 47, no. 2, 2009, pp. 247-55.
Li SY, Gilbert SA, Li Q, et al. Aldehyde dehydrogenase-2 (ALDH2) ameliorates chronic alcohol ingestion-induced myocardial insulin resistance and endoplasmic reticulum stress. J Mol Cell Cardiol. 2009;47(2):247-55.
Li, S. Y., Gilbert, S. A., Li, Q., & Ren, J. (2009). Aldehyde dehydrogenase-2 (ALDH2) ameliorates chronic alcohol ingestion-induced myocardial insulin resistance and endoplasmic reticulum stress. Journal of Molecular and Cellular Cardiology, 47(2), 247-55. https://doi.org/10.1016/j.yjmcc.2009.03.017
Li SY, et al. Aldehyde Dehydrogenase-2 (ALDH2) Ameliorates Chronic Alcohol Ingestion-induced Myocardial Insulin Resistance and Endoplasmic Reticulum Stress. J Mol Cell Cardiol. 2009;47(2):247-55. PubMed PMID: 19344727.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aldehyde dehydrogenase-2 (ALDH2) ameliorates chronic alcohol ingestion-induced myocardial insulin resistance and endoplasmic reticulum stress. AU - Li,Shi-Yan, AU - Gilbert,Sara A B, AU - Li,Qun, AU - Ren,Jun, Y1 - 2009/04/01/ PY - 2009/01/20/received PY - 2009/03/23/revised PY - 2009/03/24/accepted PY - 2009/4/7/entrez PY - 2009/4/7/pubmed PY - 2009/9/3/medline SP - 247 EP - 55 JF - Journal of molecular and cellular cardiology JO - J. Mol. Cell. Cardiol. VL - 47 IS - 2 N2 - Chronic alcohol intake leads to insulin resistance and alcoholic cardiomyopathy, which appears to be a result of the complex interaction between genes and environment. This study was designed to examine the impact of aldehyde dehydrogenase-2 (ALDH2) transgenic overexpression on alcohol-induced insulin resistance and myocardial injury. ALDH2 transgenic mice were produced using chicken beta-actin promoter. Wild-type FVB and ALDH2 mice were fed a 4% alcohol or control diet for 12 weeks. Cell shortening was evaluated using an edge-detection system. Western blot analysis was used to assess insulin signaling at the levels of receptor, IRS, Akt, GSK-3beta, the transcription factors Foxo3a, c-Jun amino-terminal kinase (JNK) and c-Jun. Chronic alcohol intake led to glucose intolerance, reduced glucose uptake, cardiac hypertrophy and reduced cell shortening, the effects of which were alleviated by ALDH2. ALDH2 significantly attenuated alcohol-induced decrease in the insulin-stimulated tyrosine phosphorylation and increase in serine phosphorylation of IRS. Phosphorylation of Akt, GSK-3beta and Foxo3a was reduced following alcohol intake, the effect of which was abrogated by ALDH2. Levels of JNK, c-Jun and their phosphorylation were elevated following chronic alcohol intake, which were obliterated by ALDH2. Transfection of H9C2 myoblast cells with Foxo3a adenovirus mimicked acetaldehyde-induced JNK activation and glucose uptake defect whereas the dominant negative Foxo3a ablated acetaldehyde-elicited insulin insensitivity. In addition, ALDH2 reversed alcohol-induced myocardial ER stress. These data revealed that ALDH2 overexpression antagonizes chronic alcohol intake-induced cardiac insulin insensitivity and contractile defect, possibly via improvement of insulin signaling at the levels of insulin receptor, IRS, Akt, Foxo3a and JNK. SN - 1095-8584 UR - https://www.unboundmedicine.com/medline/citation/19344727/Aldehyde_dehydrogenase_2__ALDH2__ameliorates_chronic_alcohol_ingestion_induced_myocardial_insulin_resistance_and_endoplasmic_reticulum_stress_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-2828(09)00142-4 DB - PRIME DP - Unbound Medicine ER -