Altered SR protein expression associated with contractile dysfunction in diabetic rat hearts.
The goal of this study was to examine whether alteration of sarcoplasmic reticulum (SR) protein levels is associated with early-onset diastolic and late-onset systolic dysfunction in streptozotocin (STZ)-induced diabetic rat hearts. Four-week diabetic rat hearts exhibited slow relaxation, whereas 6-wk diabetic rat hearts exhibited slow and depressed contraction. Total phospholamban level was increased, and phosphorylated level was decreased in 4- and 6-wk diabetic rat hearts. Sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2) protein level was unchanged in 4-wk but decreased in 6-wk diabetic rat hearts. Only the apparent affinity of SR Ca2+ uptake for Ca2+ was decreased in 4-wk diabetic rat hearts, but the apparent affinity and the maximum rate was decreased in 6-wk diabetic rat hearts. Insulin treatment of the diabetic rats normalized SR protein expression and function. It was concluded that an increase in nonphosphorylated phospholamban and a decrease in the apparent affinity of SR Ca2+ pump for Ca2+ are associated with early-onset diastolic dysfunction and decreases in SERCA2 protein level and apparent affinity and maximum velocity of SR Ca2+ pump are associated with late-onset systolic dysfunction in diabetic rats.
Zhong
Y
Y
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0575, USA.
Ahmed
S
S
Grupp
I L
IL
Matlib
M A
MA
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight; D002118:Calcium / Q000378:metabolism / Q000493:pharmacokinetics; D002135:Calcium-Binding Proteins / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D003971:Diastole; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006339:Heart Rate; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects; D009929:Organ Size; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013311:Streptozocin; D000099211:Phospholamban
D001786:Blood Glucose; D002118:Calcium; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D007328:Insulin; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013311:Streptozocin; D000099211:Phospholamban; C506948:Atp2a2 protein, rat