title: Regulation of apoptosis and autophagy by sphingosylphosphorylcholine in vascular endothelial cells.
abstract: Sphingosylphosphorylcholine (SPC), an important cardiovascular mediator derived from sphingomyelin that has atheroprotective effects via actions on vascular endothelial cells (VECs) at normal levels in vivo. However, the underlying mechanism is not well known. To clarify this question, we first investigated the effect of SPC on VEC apoptosis and autophagy induced by deprivation of serum and fibroblast growth factor 2 (FGF-2). SPC at 5-20 µM inhibited apoptosis and induced autophagy in vitro. To understand the underlying mechanism, we investigated the role of integrin β4 in SPC-induced autophagy in VECs. SPC significantly decreased the level of integrin β4, whereas overexpression of integrin β4 inhibited SPC-induced autophagy. Moreover, knockdown of integrin β4 promoted VEC autophagy. To understand the downstream factors of integrin β4 in this process, we observed the effects of SPC on phosphatidylcholine-specific phospholipase C (PC-PLC) activity and level of p53. PC-PLC activity and p53 level in cytoplasm was decreased during autophagy induced by SPC, and knockdown of integrin β4 inhibited the activity of PC-PLC and the cytoplasmic level of p53. SPC may promote autophagy via integrin β4. Moreover, PC-PLC and p53 may be the downstream factors of integrin β4 in autophagy of VECs deprived of serum and FGF-2.
authors.affiliation: Institute of Developmental Biology, School of Life Science, Shandong University, Jinan, China.
authors.forename: Di
authors.initials: D
authors.lastname: Ge
authors.forename: Qingchuan
authors.initials: Q
authors.lastname: Jing
authors.forename: Ning
authors.initials: N
authors.lastname: Meng
authors.forename: Le
authors.initials: L
authors.lastname: Su
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shangli
authors.initials: S
authors.lastname: Zhang
authors.forename: Junying
authors.initials: J
authors.lastname: Miao
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D039663:Integrin beta4 / Q000378:metabolism; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: C059834:ITGB4 protein, human; D039663:Integrin beta4; D016159:Tumor Suppressor Protein p53; C005356:sphingosine phosphorylcholine; D016222:Fibroblast Growth Factor 2; D010767:Phosphorylcholine; D010738:Type C Phospholipases; C105598:phosphatidylcholine-specific phospholipase C; D013110:Sphingosine