| Wu Lee-Pin |
------>authors3_c= ------>paper_class1=4 ------>Impact_Factor=None ------>paper_class3=0 ------>paper_class2=0 ------>vol= ------>confirm_bywho=clin ------>insert_bywho=pin ------>Jurnal_Rank=None ------>authors4_c= ------>comm_author= ------>patent_EDate=None ------>authors5_c= ------>publish_day=1 ------>paper_class2Letter=None ------>page2=47 ------>medlineContent= ------>unit=H0100 ------>insert_date=20081128 ------>iam=1 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN=978986194 ------>authors_c=??? ------>score=-39 ------>journal_name=????????JCI ???? ------>paper_name=JCI ???? ------>confirm_date=20090605 ------>tch_id=086023 ------>pmid=19920353 ------>page1=?45 ------>fullAbstract=In noncontractile cells, increases in intracellular Ca2+ concentration serve as a second messenger to signal proliferation, differentiation, metabolism, motility, and cell death. Many of these Ca2+-dependent regulatory processes operate in cardiomyocytes, although it remains unclear how Ca2+ serves as a second messenger given the high Ca2+ concentrations that control contraction. T-type Ca2+ channels are reexpressed in adult ventricular myocytes during pathologic hypertrophy, although their physiologic function remains unknown. Here we generated cardiac-specific transgenic mice with inducible expression of alpha1G, which generates Cav3.1 current, to investigate whether this type of Ca2+ influx mechanism regulates the cardiac hypertrophic response. Unexpectedly, alpha1G transgenic mice showed no cardiac pathology despite large increases in Ca2+ influx, and they were even partially resistant to pressure overload-, isoproterenol-, and exercise-induced cardiac hypertrophy. Conversely, alpha1G-/- mice displayed enhanced hypertrophic responses following pressure overload or isoproterenol infusion. Enhanced hypertrophy and disease in alpha1G-/- mice was rescued with the alpha1G transgene, demonstrating a myocyte-autonomous requirement of alpha1G for protection. Mechanistically, alpha1G interacted with NOS3, which augmented cGMP-dependent protein kinase type I activity in alpha1G transgenic hearts after pressure overload. Further, the anti-hypertrophic effect of alpha1G overexpression was abrogated by a NOS3 inhibitor and by crossing the mice onto the Nos3-/- background. Thus, cardiac alpha1G reexpression and its associated pool of T-type Ca2+ antagonize cardiac hypertrophy through a NOS3-dependent signaling mechanism. ------>tmu_sno=None ------>sno=20093 ------>authors2= ------>authors3= ------>authors4= ------>authors5= ------>authors6= ------>authors6_c= ------>authors=Wu Lee-Pin ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=alpha1G-dependent T-type Ca2+ current antagonizes cardiac hypertrophy through a NOS3-dependent mechanism in mice. ------>language=1 ------>check_flag=None ------>submit_date=None ------>country=NULL ------>no= ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2008 ------>submit_flag=None ------>publish_month=5 |