Preconditioning prevents alterations in cardiac SR gene expression due to ischemia-reperfusion.
We have previously shown that ischemic preconditioning (IP) improves cardiac performance and sarcoplasmic reticulum (SR) function in hearts subjected to ischemia-reperfusion (I/R). In this study, we examined the effect of IP on I/R-induced changes in gene expression for SR proteins such as the Ca(2+) release channel, Ca(2+) pump ATPase, phospholamban, and calsequestrin in the isolated rat heart. Normal isolated rat hearts exposed to three brief cycles of IP (5-min ischemia and 5-min reperfusion) exhibited a significant decrease in the transcript levels of SR genes. Nonpreconditioned I/R hearts when subjected to 30-min ischemia and 30-min reperfusion showed a marked decrease in mRNA levels for the SR proteins compared with normal hearts; this decrease was attenuated by preconditioning. Although hearts subjected to Ca(2+) paradox (CP) have been shown to exhibit intracellular Ca(2+) overload and SR dysfunction like those in I/R hearts, virtually nothing is known regarding the effect of CP on cardiac SR gene expression. Accordingly, CP (5-min Ca(2+)-free perfusion and 30-min reperfusion with normal medium) was observed to produce dramatic changes in SR gene expression, and the heart failed to contract; these alterations were attenuated by IP. Our results show that 1) both I/R and CP depress SR gene expression in the normal heart, 2) IP attenuates I/R- and CP-induced depression in cardiac function and SR gene expression, and 3) intracellular Ca(2+) overload may play a role in depressing SR gene expression in both I/R and CP hearts.
Temsah
Rana M
RM
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada R2H 2A6.
Kawabata
Kenichi
K
Chapman
Donald
D
Dhalla
Naranjan S
NS
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology*; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013997:Time Factors; D016277:Ventricular Function, Left / Q000502:physiology
D019837:Ryanodine Receptor Calcium Release Channel; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases