Diminished expression of sarcoplasmic reticulum Ca(2+)-ATPase and ryanodine sensitive Ca(2+)Channel mRNA in streptozotocin-induced diabetic rat heart.
The diabetic heart has an abnormal intracellular calcium ([Ca(2+)]i) metabolism. However, the responsible molecular mechanisms are unclear. The present study aimed to investigate mRNAs expressed in the proteins which regulate heart [Ca(2+)]i metabolism in streptozotocin (STZ)-induced diabetic rats. Expression of sarcoplasmic reticulum Ca(2+)-adenosine triphosphatase (SR Ca(2+)-ATPase) mRNA was significantly less in the heart 3 weeks after STZ injection than that in the age-matched controls. Together with the down-regulation of SR Ca(2+)-ATPase, expression of ryanodine sensitive Ca(2+)channel (RYR) mRNA was also decreased 12 weeks after STZ injection. Insulin supplementation fully restored the decreased mRNAs expression of SR Ca(2+)-ATPase and RYR. The diminished expression and restoration with insulin supplementation of SR Ca(2+)-ATPase was further confirmed at the protein level. In contrast, expression of mRNAs coding the L-type Ca(2+)channel, Na(+)-Ca(2+)exchanger, or phospholamban were not affected 3 or 12 weeks after STZ injection. These results can be taken to indicate that the down-regulation of SR Ca(2+)-ATPase and RYR mRNAs is a possible underlying cause of cardiac dysfunction in STZ-induced diabetic rats.
Teshima
Y
Y
Department of Internal Medicine I, School of Medicine, Oita, 879-5593, Japan.
Takahashi
N
N
Saikawa
T
T
Hara
M
M
Yasunaga
S
S
Hidaka
S
S
Sakata
T
T
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000235:genetics*; D003921:Diabetes Mellitus, Experimental; D005786:Gene Expression Regulation; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D012333:RNA, Messenger; D051381:Rats; D017208:Rats, Wistar; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D012519:Sarcoplasmic Reticulum / Q000201:enzymology*; D013311:Streptozocin
D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger; D019837:Ryanodine Receptor Calcium Release Channel; D013311:Streptozocin; D000252:Calcium-Transporting ATPases; D002118:Calcium