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• W2887050348 abstract "Abstract—Doxorubicin (DOX)–induced cardiomyopathy has been found to be associated with impaired Ca2+ handling in the sarcoplasmic reticulum (SR), leading to reduced cardiac function. We have recently demonstrated that expression of mRNA encoding sarco(endo)plasmic reticulum Ca2+-ATPase 2 (SERCA2), a major Ca2+ transport protein in SR, is markedly decreased in DOX-treated hearts. To extend this observation, we have dissected the molecular mechanisms by which DOX downregulates SERCA2 gene transcription. Using cultured rat neonatal cardiac myocytes, we found that the antioxidant N-acetylcysteine blocked the DOX-induced decrease in SERCA2 mRNA levels, as well as the DOX-induced increase in H2O2 concentration; thus, H2O2 is an intracellular mediator of DOX activity. Using a luciferase reporter assay, we found that the sequence from −284 to −72 bp in the 5′ flanking region of the SERCA2 gene has a DOX-responsive element. Although several transcription factors have putative binding motifs in this region of the S..." @default.
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• W2887050348 date "2000-01-07" @default.
• W2887050348 modified "2023-09-23" @default.
• W2887050348 title "Mechanism of Doxorubicin-Induced Inhibition of Sarcoplasmic Reticulum Ca2+-ATPase Gene Transcription" @default.
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