title: Suppressive effect of exogenous carbon monoxide on endotoxin-stimulated platelet over-activation via the glycoprotein-mediated PI3K-Akt-GSK3β pathway.
abstract: Platelet activation is an important event involved in the pathophysiological processes of the coagulation system. Clinical evidence has shown that platelets undergo distinctive pathological processes during sepsis. Unfortunately, how platelets physiologically respond to inflammation or sepsis is not well understood. In this study, we used a lipopolysaccharide (LPS)-stimulated platelet model to systemically investigate alterations in membrane glycoprotein expression, molecular signaling, morphology and critical functions of platelets. We found that platelet adhesion, aggregation, secretion, and spreading on immobilized fibrinogen and the expression of platelet membrane glycoproteins were significantly increased by LPS stimulation, and these changes were accompanied by a significant decrease in cGMP levels and an abnormal distribution of platelet α-granules. Exogenous CO reversed these alterations. Profound morphological changes in LPS-stimulated platelets were observed using atomic force microscopy and phase microscopy. Furthermore, the elevated activities of PI3Ks, AKt and GSK-3β were effectively suppressed by exogenous CO, leading to the improvement of platelet function. Together, these results provide evidence that platelet over-activation persists under LPS-stimulation and that exogenous CO plays an important role in suppressing platelet activation via the glycoprotein-mediated PI3K-Akt-GSK3β pathway.
authors.affiliation: Department of Critical Care Medicine, Affiliated Hospital, Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Dadong
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Burns and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Burns and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Weiting
authors.initials: W
authors.lastname: Qin
authors.affiliation: Department of Burns and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Jingjia
authors.initials: J
authors.lastname: Chen
authors.affiliation: School of Science, Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Burns and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Zhuang
authors.affiliation: Department of Burns and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Bingwei
authors.initials: B
authors.lastname: Sun
mesh_terms: D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D015153:Blotting, Western; D002248:Carbon Monoxide / Q000378:metabolism / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D039421:Integrin alpha2; D008070:Lipopolysaccharides / Q000494:pharmacology*; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009942:Organometallic Compounds / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015539:Platelet Activation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D006023:Glycoproteins; D039421:Integrin alpha2; D008070:Lipopolysaccharides; D009942:Organometallic Compounds; C447082:tricarbonyldichlororuthenium (II) dimer; D002248:Carbon Monoxide; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D006152:Cyclic GMP