title: Overexpression of Shp-2 attenuates apoptosis in neonatal rat cardiac myocytes through the ERK pathway.
abstract: During cardiac ischemia and end-stage heart disease, a large number of cardiac cells are apoptotic, and therefore, heart function is impaired. Although the role of Shp-2 in cell survival has been reported, its regulation of cardiac apoptosis is still undetermined. To better understand the potential role of Shp-2 in apoptosis, cell death was determined in serum-depleted cardiomyocytes. Shp-2 was inhibited by NSC87877, and apoptosis, Cyt C release and caspase 3 activation were determined. To evaluate the notion that Shp-2 plays a role in survival stimulation, wild-type and gain-of-function mutant Shp-2 adenoviruses were infected into neonatal cardiomyocytes, and ERK activation was examined. Finally, the MEK inhibitor U0126 was utilized to block the ERK pathway and determine the role of Shp-2 in this pathway. We found that Shp-2 inhibition enhanced apoptosis via regulation of mitochondrial Cyt C release and activation of caspase 3. Overexpression of Shp-2 inhibited apoptosis through activation of ERK. The MEK inhibitor U0126 abolished Shp-2's effect on apoptosis in cardiomyocytes. Our results have revealed that Shp-2 functions as an intracellular inhibitor of apoptosis. These data provide insight into the pathogenesis and the therapeutic strategies of heart diseases.
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin 150086, China.
authors.forename: Guoyuan
authors.initials: G
authors.lastname: Wang
authors.forename: Chengyan
authors.initials: C
authors.lastname: Jin
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Hou
authors.forename: Lijing
authors.initials: L
authors.lastname: Zhang
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.forename: Luquan
authors.initials: L
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Wu
authors.forename: Quanfeng
authors.initials: Q
authors.lastname: Li
authors.forename: Changqing
authors.initials: C
authors.lastname: Xu
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002070:Butadienes / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D045304:Cytochromes c / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation
chemical_list: D002070:Butadienes; D004791:Enzyme Inhibitors; C512715:NSC-87877; D009570:Nitriles; D011804:Quinolines; C113580:U 0126; D045304:Cytochromes c; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; C516727:Ptpn11 protein, rat; C505410:Casp3 protein, rat; D053148:Caspase 3