Improvement of defective sarcoplasmic reticulum Ca2+ transport in diabetic heart of transgenic rats expressing the human kallikrein‐1 gene

The bradykinin‐forming enzyme kallikrein‐1 is expressed in the heart. To examine whether contractile performance and sarcoplasmic reticulum Ca2+ transport of the diabetic heart can be rescued by targeting the kallikrein‐kinin system, we studied left ventricular function and sarcoplasmic reticular Ca...

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Published in:The FASEB journal 2004-12, Vol.18 (15), p.1967-1969
Main Authors: Tschöpe, Carsten, Spillmann, Frank, Rehfeld, Uwe, Koch, Matthias, Westermann, Dirk, Altmann, Christine, Dendorfer, Andreas, Walther, Thomas, Bader, Michael, Paul, Martin, Schultheiss, Heinz‐Peter, Vetter, Roland
Format: Article
Language:English
Subjects:
Animals
Animals, Genetically Modified
bradykinin
Calcium - metabolism
Calcium-Binding Proteins - metabolism
Calcium-Transporting ATPases - metabolism
cardiomyopathy
diabetes mellitus
Diabetes Mellitus, Experimental - metabolism
Diabetes Mellitus, Experimental - physiopathology
Gene Expression
Humans
Ion Transport
Myocardium - metabolism
phospholamban phosphorylation
Phosphorylation
Rats
Sarcoplasmic Reticulum - metabolism
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Tissue Kallikreins - genetics
Tissue Kallikreins - metabolism
Ventricular Function, Left
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Summary:The bradykinin‐forming enzyme kallikrein‐1 is expressed in the heart. To examine whether contractile performance and sarcoplasmic reticulum Ca2+ transport of the diabetic heart can be rescued by targeting the kallikrein‐kinin system, we studied left ventricular function and sarcoplasmic reticular Ca2+ uptake after induction of streptozotocin‐induced diabetes mellitus in transgenic rats expressing the human tissue kallikrein‐1 gene. Six weeks after a single injection of either streptozotocin (70 mg/kg ip) or vehicle, left ventricular performance was determined using a Millar‐Tip catheter system. The Ca2+‐transporting activity of reticulum‐derived membrane vesicles was determined in left ventricular homogenates as oxalate‐supported 45Ca2+ uptake. Western blot analysis was used to quantify the reticular Ca2+‐ATPase SERCA2a, phospholamban, and the phosphorylation status of the latter. Contractile performance and Ca2+ uptake activity were similar in nondiabetic wild‐type and transgenic rats. Severely diabetic wild‐type animals exhibited impaired left ventricular performance and decreased reticular Ca2+ uptake (‐39% vs. wild‐type rats, P
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.04-1614fje