Valsartan Protects Against ER Stress-Induced Myocardial Apoptosis via CHOP/Puma Signaling Pathway in Streptozotocin-Induced Diabetic Rats

Eur J Pharm Sci. 2011 Apr 18;42(5):496-502. doi: 10.1016/j.ejps.2011.02.005. Epub 2011 Feb 21.

Abstract

Recently studies indicated that valsartan could prevent the progression of heart failure caused by diabetic cardiomyopathy (DCM), while the mechanisms were still poorly understood. The present study was designed to investigate whether valsartan could reduce the endoplasmic reticulum (ER) stress and DCM-induced cardiac remodeling. Our data has shown that valsartan can ameliorate ER stress-induced cardiac remodeling and myocardial apoptosis in DCM rats. By using of immunofluorescence and RT-PCR, valsartan has been found to play a protective role via down-regulating the expression of transcriptional induction of C/EBP homologous protein (CHOP) and p53 upregulated modulator of apoptosis (Puma), two crucial factors known to be implicated in the ER stress-induced myocardial apoptosis. And the expression level of Puma was closely related to CHOP. Thus, our experiment strongly suggests that the administration of valsartan can ameliorate the ER stress through blocking the activation of CHOP/Puma signaling pathway, which provides a new insight into the potential molecular mechanism of cardiomyocyte apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / administration & dosage
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Animals
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism*
  • Blotting, Western
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetic Cardiomyopathies / metabolism
  • Diabetic Cardiomyopathies / pathology
  • Diabetic Cardiomyopathies / prevention & control
  • Endoplasmic Reticulum / drug effects*
  • Endoplasmic Reticulum / metabolism
  • Fluorescent Antibody Technique
  • Male
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Tetrazoles / administration & dosage
  • Tetrazoles / therapeutic use*
  • Transcription Factor CHOP / metabolism*
  • Valine / administration & dosage
  • Valine / analogs & derivatives*
  • Valine / therapeutic use
  • Valsartan
  • Ventricular Remodeling / drug effects

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Apoptosis Regulatory Proteins
  • Bbc3 protein, rat
  • Ddit3 protein, rat
  • Tetrazoles
  • Transcription Factor CHOP
  • Valsartan
  • Valine