RGD Reference Report - Dominant negative p38{alpha} mitogen-activated protein kinase prevents cardiac apoptosis and remodeling after streptozotocin-induced diabetes mellitus.

General

Dominant negative p38{alpha} mitogen-activated protein kinase prevents cardiac apoptosis and remodeling after streptozotocin-induced diabetes mellitus.
Authors:	Thandavarayan, RA Watanabe, K Ma, M Gurusamy, N Veeraveedu, PT Konishi, T Zhang, S Muslin, AJ Kodama, M Aizawa, Y
Citation:	Thandavarayan RA, etal., Am J Physiol Heart Circ Physiol. 2009 Jul 17.
RGD ID:	2311565
Pubmed:	PMID:19617408 (View Abstract at PubMed)
DOI:	DOI:10.1152/ajpheart.00124.2009 (Journal Full-text)
The p38 mitogen-activated protein kinase (MAPK) is activated during heart diseases that might associate with myocardial damage and cardiac remodeling process. Diabetic cardiomyopathy is associated with increased oxidative stress and inflammation. The purpose of this study was to investigate the role of p38alpha MAPK after experimental diabetes by using transgenic mice with cardiac-specific expression of a dominant-negative mutant form of p38alpha MAPK (TG). The elevation of blood glucose was comparable between the nontransgenic (NTG) and TG mice. The expression of phospho-p38 MAPK and phospho-MAPKAPK-2 levels were significantly suppressed in TG mice heart than in NTG mice after diabetes induction. Left ventricular (LV) dimension in systole was smaller and the percent fractional shortening was higher in diabetic TG mice compared with diabetic NTG mice. In addition, diabetic TG mice had reduced cardiac myocyte diameter, content of cardiac fibrosis, LV tissue expressions of atrial natriuretic peptide, transforming growth factor beta1, and collagen III compared to diabetic NTG mice. Moreover, LV expression of NADPH oxidase subunits, p22 phox, p67 phox, gp91 phox and Nox4, Reactive oxygen species and lipid peroxidation levels were significantly increased in diabetic NTG mice but not in diabetic TG mice. Furthermore, myocardial apoptosis, the number of caspase-3 positive cells and the downregulation of anti-apoptotic protein Bcl-XL were less in diabetic TG mice compared to diabetic NTG mice. In conclusion, our data establish that p38alpha MAPK activity is required for cardiac remodeling after diabetes induction and suggest that p38alpha MAPK may promote cardiomyocyte apoptosis by downregulation of Bcl-XL. Key words: p38 MAPK, Diabetic cardiomyopathy, oxidative stress, Apoptosis.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
heart disease		ISO	Mapk14 (Mus musculus)	2311565; 2311565	associated with Diabetes Mellitus and Experimental	RGD
heart disease		IMP		2311565	associated with Diabetes Mellitus and Experimental	RGD

Objects Annotated

Genes (Rattus norvegicus)

Mapk14 (mitogen activated protein kinase 14)

Genes (Mus musculus)

Mapk14 (mitogen-activated protein kinase 14)

Genes (Homo sapiens)

MAPK14 (mitogen-activated protein kinase 14)

Objects referenced in this article

Gene	Madcam1	mucosal vascular addressin cell adhesion molecule 1	Mus musculus

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Dominant negative p38{alpha} mitogen-activated protein kinase prevents cardiac apoptosis and remodeling after streptozotocin-induced diabetes mellitus.