Sarcoplasmic reticulum genes are upregulated in mild cardiac hypertrophy but downregulated in severe cardiac hypertrophy induced by pressure overload.
|
| Abstract |
Changes in contractile and relaxation properties of heart muscle in the cardiac hypertrophy induced by pressure overload have been attributed to alterations in intracellular Ca2+ transport as well as the phenotypic and quantitative changes in contractile protein. However, contradictory data have been reported regarding Ca2+ uptake, release and storage by the sarcoplasmic reticulum (SR). The purpose of this study was to evaluate the changes in SR Ca(2+)-ATPase, ryanodine receptor, calsequestrin and alpha-actin gene expression, and the changes in Ca2+ uptake capacity in various degrees of hypertrophied hearts due to pressure overload. Cardiac hypertrophy was produced in rats by placing a constricting clip (0.80 mm) around the suprarenal abdominal aorta for 8 days. The mRNA levels and Ca2+ uptake capacity were then measured as a function of the severity of cardiac hypertrophy. Ca(2+)-ATPase and ryanodine receptor mRNA levels were increased in mildly hypertrophied hearts but were diminished in severely hypertrophied hearts, showing a bimodal response to pressure overload, Ca2+ uptake capacity showed similar changes along with a positive correlation with Ca(2+)-ATPase mRNA level (r = 0.67, P < 0.001). In contrast, the level of calsequestrin mRNA expression was unaltered and that of alpha-actin was markedly increased over a range of severity of cardiac hypertrophy. These findings suggest that the expression of sarcoplasmic reticulum genes for Ca2+ uptake and release is up- or downregulated dependent on the degree of pressure overload. The gene for the SR Ca2+ storage protein, calsequestrin, might be under different control from these genes in pressure overload. Our findings suggest that the decrease in ratio of mRNAs encoding Ca2+ uptake and release proteins to those encoding contractile proteins could significantly contribute to the slowed contractile and relaxation properties seen in pressure-overloaded hearts.
|
|---|---|
| Authors | M Arai, T Suzuki, R Nagai |
| Journal | Journal of molecular and cellular cardiology (J Mol Cell Cardiol) Vol. 28 Issue 8 Pg. 1583-90 (Aug 1996) ISSN: 0022-2828 [Print] England |
| PMID | 8877769 (Publication Type: Comparative Study, Journal Article) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!