T. Takizawa, M. Arai, A. Yoguchi, K. Tomaru, M. Kurabayashi and R. Nagai. Transcription of the SERCA2 Gene is Decreased in Pressure-overloaded Hearts: A Study Using In Vivo Direct Gene Transfer into Living Myocardium. Journal of Molecular and Cellular Cardiology (1999) 31, 2167-2174. The sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) controls the myocardial relaxation process. Under pressure-overload, the expression of its mRNA decreases, thus controlling cardiac function to conform to the load. However, it is not known whether this decreased expression is caused by a decrease in the transcription of the SERCA2 gene. The object of this study was to determine the transcription control mechanism of the SERCA2 gene under pressure-overload in vivo, and to identify the pressure-overload-sensitive regions of the SERCA2 gene. Ten micrograms of a plasmid, containing the 5' upstream (-1810 bp to +350 bp) region of the SERCA2 gene and a luciferase reporter gene, were introduced into adult rat myocardium by in vivo direct gene transfer, and the luciferase activity was measured 5 days later. The transcriptional activity under pressure-overload decreased to 27+/-17% of the control. Based on this result, we concluded that the decreased mRNA expression of SERCA2 in pressure-overload cardiac hypertrophy is due to decreased gene transcription. In addition, various deletion fragments of the SERCA2 promoter region were produced, and tested for luciferase production under pressure-overload. Our data suggest that a transcription activation site is present between -685 and -284 bp, and two transcription inhibition sites are present between -1810 to -1110 bp and -284 to -72 bp. These may be the pressure-sensitive regions of the SERCA2 gene of in vivo hypertrophied myocardium under pressure-overload.
Copyright 1999 Academic Press.