【摘 要】
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Dilated cardiomyopathy(DCM)is a severe disorder caused by medications or genetic mutations.D5 dopamine receptor(D5R)gene knockout(D5-/-)mice have cardiac hypertrophy and high blood pressure.To investi
【机 构】
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Institute of Laboratory Animal Science,Chinese Academy of Medical Sciences(CAMS)& Comparative Medici
论文部分内容阅读
Dilated cardiomyopathy(DCM)is a severe disorder caused by medications or genetic mutations.D5 dopamine receptor(D5R)gene knockout(D5-/-)mice have cardiac hypertrophy and high blood pressure.To investigate the role and mechanism by which the D5R regulates cardiac function,we generated cardiac-specific human D5R F173L(hD5F173L-TG)and cardiac-specific human D5R wild-type(hD5WT-TG)transgenic mice,and H9c2 cells stably expressing hD5F173L and hD5WT.We found that cardiac-specific hD5F173L-TG mice,relative to hD5WT-TG mice,presented with DCM and increased cardiac expression of NOX2 and increased activities of NADPH oxidase,ERK1/2,and AKT that were ameliorated by the NADPH oxidase inhibitor apocynin.NOX2 expression and ERK1/2 and AKT activities were also higher in H9c2-hD5F173L than H9c2-hD5WT cells.Protein kinase G rather than protein kinase A was involved in the D5R-mediated inhibition of NADPH oxidase and ERK1/2 and AKT pathways.We suggest that the D5R may play an important role in the preservation of normal heart function by inhibiting the production of reactive oxygen species via a protein kinase G,ERK1/2,and AKT pathway.
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