title: PAI1: a novel PP1-interacting protein that mediates human plasma's anti-apoptotic effect in endothelial cells.
abstract: Activation of apoptotic signalling in endothelial cells contributes to the detrimental effects of a variety of pathological stimuli. In investigating the molecular events underlying the anti-apoptotic effect of human plasma in cultured human endothelial cells, we unexpectedly uncovered a novel mechanism of apoptosis suppression by human plasma through an interaction between two previously unrelated proteins. Human plasma inhibited hypoxia-serum deprivation-induced apoptosis and stimulated BADS136and AktS473phosphorylation. Akt1 silencing reversed part (~52%) of the anti-apoptotic effect of human plasma, suggesting the existence of additional mechanisms mediating the anti-apoptotic effect other than Akt signalling. Human plasma disrupted the interaction of BAD with protein phosphatase 1 (PP1). Mass spectrometry identified fourteen PP1-interacting proteins induced by human plasma. Notably, a group of serine protease inhibitors including plasminogen activator inhibitor 1 (PAI1), a major inhibitor of fibrinolysis, were involved. Silencing of PAI1 attenuated the anti-apoptotic effect of human plasma. Furthermore, combined Akt1 and PAI1 silencing attenuated the majority of the anti-apoptotic effect of human plasma. We conclude that human plasma protects against endothelial cell apoptosis through sustained BAD phosphorylation, which is achieved by, at least in part, a novel interaction between PP1 with PAI1.
authors.affiliation: Department of Pathology, Hunan Normal University Medical College, Changsha, Hunan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yao
authors.affiliation: Department of Pathology, Hunan Normal University Medical College, Changsha, Hunan, China.
authors.forename: Guangchun
authors.initials: G
authors.lastname: He
authors.affiliation: Department of Pathology, Hunan Normal University Medical College, Changsha, Hunan, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Pathology, Hunan Normal University Medical College, Changsha, Hunan, China.
authors.forename: Shichao
authors.initials: S
authors.lastname: Yan
authors.affiliation: Department of Pathology, Hunan Normal University Medical College, Changsha, Hunan, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Pediatrics, Hunan Normal University Medical College, Changsha, Hunan, China.
authors.forename: Liujiang
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Medicine, Baylor College of Medicine and Center for Translational Research on Inflammatory Diseases (CTRID), Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC), Houston, TX, USA.
authors.forename: K Vinod
authors.initials: KV
authors.lastname: Vijayan
authors.affiliation: Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.|Department of General Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of General Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Department of General Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xiongying
authors.initials: X
authors.lastname: Miao
authors.affiliation: Department of Pathology, Hunan Normal University Medical College, Changsha, Hunan, China.
authors.forename: Xiyun
authors.initials: X
authors.lastname: Deng
mesh_terms: D017209:Apoptosis; D015687:Cell Hypoxia; D019610:Cytoprotection; D042783:Endothelial Cells / Q000378:metabolism*; D020868:Gene Silencing; D006801:Humans; D008954:Models, Biological; D010766:Phosphorylation; D010949:Plasma / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011485:Protein Binding; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000378:metabolism
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D051025:bcl-Associated Death Protein; D051057:Proto-Oncogene Proteins c-akt; D054645:Protein Phosphatase 1
keywords: PP1-interacting protein; apoptosis; endothelial cells; plasminogen activator inhibitor 1; protein phosphatase 1