title: Transcription of the SERCA2 gene is decreased in pressure-overloaded hearts: A study using in vivo direct gene transfer into living myocardium.
abstract: 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.
authors.affiliation: Second Department of Internal Medicine, Gunma University School of Medicine, Gunma, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Takizawa
authors.forename: M
authors.initials: M
authors.lastname: Arai
authors.forename: A
authors.initials: A
authors.lastname: Yoguchi
authors.forename: K
authors.initials: K
authors.lastname: Tomaru
authors.forename: M
authors.initials: M
authors.lastname: Kurabayashi
authors.forename: R
authors.initials: R
authors.lastname: Nagai
mesh_terms: D000818:Animals; D001794:Blood Pressure; D000252:Calcium-Transporting ATPases / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D018014:Gene Transfer Techniques; D006321:Heart / Q000502:physiology*; D009200:Myocardial Contraction / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic
chemical_list: D000252:Calcium-Transporting ATPases