Transgenic overexpression of the sarcoplasmic reticulum Ca(2+) ATPase improves reticular Ca(2+) handling in normal and diabetic rat hearts

Item Type:	Article
Title:	Transgenic overexpression of the sarcoplasmic reticulum Ca(2+) ATPase improves reticular Ca(2+) handling in normal and diabetic rat hearts
Creators Name:	Vetter, R. and Rehfeld, U. and Reissfelder, C. and Weiss, W. and Wagner, K.D. and Guenther, J. and Hammes, A. and Tschoepe, C. and Dillmann, W. and Paul, M.
Abstract:	Slowed relaxation in diabetic cardiomyopathy (CM) is partially related to diminished expression of the sarcoplasmic reticulum (SR) Ca(2+) -ATPase SERCA2a. To evaluate the impact of SERCA2a overexpression on SR Ca(2+) handling in diabetic CM, we 1) generated transgenic rats harboring a human cytomegalovirus enhancer/chicken {beta}-actin promotor-controlled rat ERCA2 transgene (SERCA2-TGR), 2) characterized their SR phenotype, and 3) examined whether transgene expression may rescue SR Ca(2+) transport in streptozotocin-induced diabetes. The transgene was expressed in all heart chambers. Compared to wild-type (WT) rats, a heterozygous line exhibited increased SERCA2 mRNA (1.5-fold), SERCA2 protein (+26%) and SR Ca(2+) uptake (+37%). Phospholamban expression was not altered. In SERCA2-TGR, contraction amplitude (+48%) and rates of contraction (+34%) and relaxation (+35%) of isolated apillary muscles (PM) were increased (P<0.05 vs. WT, respectively); the lusitropic and inotropic responses of PM to forskolin were stronger than in WT. In diabetic myocardium with SR dysfunction, Ca(2+) uptake and SERCA2 protein of SERCA2-TGR were 1.3-fold higher (P<0.05 vs. diabetic WT). Thus, a SERCA2 overexpression in rat heart improves Ca(2+) uptake, accelerates relaxation and compensates, in part, for depressed Ca(2+) uptake in diabetic CM. Therefore, SERCA2 expression might constitute an important therapeutic target to rescue cardiac SR Ca(2+) handling in diabetes.
Keywords:	Calcium Regulation, Relaxation, Papillary Muscle, Streptozotocin-Induced Cardiomyopathy, Animals, Rats
Source:	FASEB Journal
ISSN:	0892-6638
Publisher:	Federation of American Societies for Experimental Biology
Volume:	16
Number:	12
Page Range:	1657-1659
Date:	October 2002
Official Publication:	https://doi.org/10.1096/fj.01-1019fje
PubMed:	View item in PubMed

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