Transgenic overexpression of the sarcoplasmic reticulum Ca2+ATPase improves reticular Ca2+ handling in normal and diabetic rat hearts
| Autor: | Roland Vetter, Christoph Reissfelder, Carsten Tschöpe, Wolfgang Weiss, Annette Hammes, Uwe Rehfeld, Martin Paul, Kay-Dietrich Wagner, Wolfgang H. Dillmann, Joachim Günther |
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| Rok vydání: | 2002 |
| Předmět: |
medicine.medical_specialty
Contraction (grammar) Genotype ATPase Transgene Calcium-Transporting ATPases Biology Biochemistry Gene Expression Regulation Enzymologic Diabetes Mellitus Experimental Sarcoplasmic Reticulum Calcium-Transporting ATPases Animals Genetically Modified Diabetic cardiomyopathy Internal medicine Genetics medicine Animals Humans Molecular Biology Calcium metabolism Messenger RNA Endoplasmic reticulum Myocardium medicine.disease Myocardial Contraction Phospholamban Rats Sarcoplasmic Reticulum Endocrinology biology.protein Calcium Biotechnology |
| Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 16(12) |
| ISSN: | 1530-6860 |
| Popis: | Slowed relaxation in diabetic cardiomyopathy (CM) is partially related to diminished expression of the sarcoplasmic reticulum (SR) Ca2+-ATPase SERCA2a. To evaluate the impact of SERCA2a overexpression on SR Ca2+ handling in diabetic CM, we 1) generated transgenic rats harboring a human cytomegalovirus enhancer/chicken beta-actin promotor-controlled rat SERCA2 transgene (SERCA2-TGR), 2) characterized their SR phenotype, and 3) examined whether transgene expression may rescue SR Ca2+ 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 Ca2+ uptake (+37%). Phospholamban expression was not altered. In SERCA2-TGR, contraction amplitude (+48%) and rates of contraction (+34%) and relaxation (+35%) of isolated papillary muscles (PM) were increased (P2+ uptake and SERCA2 protein of SERCA2-TGR were 1.3-fold higher (P2+ uptake, accelerates relaxation and compensates, in part, for depressed Ca2+ uptake in diabetic CM. Therefore, SERCA2 expression might constitute an important therapeutic target to rescue cardiac SR Ca2+ handling in diabetes. |
| Databáze: | OpenAIRE |
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