title: Altered SR protein expression associated with contractile dysfunction in diabetic rat hearts.
abstract: 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.
authors.affiliation: Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0575, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhong
authors.forename: S
authors.initials: S
authors.lastname: Ahmed
authors.forename: I L
authors.initials: IL
authors.lastname: Grupp
authors.forename: M A
authors.initials: MA
authors.lastname: Matlib
mesh_terms: 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
chemical_list: 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