title: cPLA2α-mediated actin rearrangements downstream of the Akt signaling is required for Cronobacter sakazakii invasion into brain endothelial cells.
abstract: Cronobacter sakazakii (C. sakazakii) is an opportunistic pathogen that causes sepsis and meningitis in neonate. The molecular mechanism involved in the pathogenesis of C. sakazakii meningitis remains unclear. In this study, we found that C. sakazakii invasion was significantly decreased in human brain microvascular endothelial cells (HBMEC) treated with cytosolic phospholipases A(2)α (cPLA(2)α) inhibitor. Increased phosphorylation of cPLA(2)α was observed in HBMEC infected with C. sakazakii, which was prevented by treatment with cPLA(2)α inhibitor. cPLA(2)α knockdown in HBMEC significantly attenuated C. sakazakii invasion into HBMEC. Immunofluorescence demonstrated that the rearrangements of actin filaments in HBMEC induced by C. sakazakii were effectively blocked by either treatment with cPLA(2)α inhibitor or transfection with cPLA(2)α siRNA. Interestingly, we found that C. sakazakii infection promoted the aggregation of phosphorylated cPLA(2)α, which was associated with depolymerized actin filaments in HBMEC. Furthermore, our data revealed that cPLA(2)α acts downstream of Akt signaling pathway in HBMEC stimulated with C. sakazakii. Taken together, our results illustrated that cPLA(2)α-mediated actin filament rearrangements downstream of Akt activation is required for C. sakazakii invasion into brain endothelial cells.
authors.affiliation: Department of Developmental Biology, Key Laboratory of Cell Biology, Ministry of Public Health, China Medical University, Heping District, Shenyang, China.
authors.forename: Dong-Xin
authors.initials: DX
authors.lastname: Liu
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Zhao
authors.forename: Wen-Gang
authors.initials: WG
authors.lastname: Fang
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Chen
mesh_terms: D051339:Actin Depolymerizing Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D001921:Brain / Q000098:blood supply / Q000382:microbiology*; D002478:Cells, Cultured; D044083:Cronobacter sakazakii / Q000472:pathogenicity*; D004730:Endothelium, Vascular / Q000382:microbiology*; D004756:Enterobacteriaceae Infections / Q000378:metabolism*; D054513:Group IV Phospholipases A2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D055806:Microvessels / Q000382:microbiology; D009894:Opportunistic Infections / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D051057:Proto-Oncogene Proteins c-akt; D054513:Group IV Phospholipases A2; C516389:PLA2G4A protein, human