title: Microparticle formation by platelets exposed to high gas pressures - An oxidative stress response.
abstract: This investigation explored the mechanism for microparticles (MPs) production by human and murine platelets exposed to high pressures of inert gases. Results demonstrate that MPs production occurs via an oxidative stress response in a dose-dependent manner and follows the potency series N2>Ar>He. Gases with higher van der Waals volumes or polarizability such as SF6and N2O, or hydrostatic pressure, do not cause MPs production. Singlet O2is generated by N2, Ar and He, which is linked to NADPH oxidase (NOX) activity. Progression of oxidative stress involves activation of nitric oxide synthase (NOS) leading to S-nitrosylation of cytosolic actin. Exposure to gases enhances actin filament turnover and associations between short actin filaments, NOS, vasodilator-stimulated phosphoprotein (VASP), focal adhesion kinase (FAK) and Rac1. Inhibition of NOS or NOX by chemical inhibitors or using platelets from mice lacking NOS2 or the gp91phox component of NOX diminish generation of reactive species, enhanced actin polymerization and MP generation by high pressure gases. We conclude that by initiating a sequence of progressive oxidative stress responses high pressure gases cause platelets to generate MPs.
authors.affiliation: Department of Emergency Medicine, University of Maryland, Baltimore, MD 21201, United States.
authors.forename: Jasjeet
authors.initials: J
authors.lastname: Bhullar
authors.affiliation: Department of Emergency Medicine, University of Maryland, Baltimore, MD 21201, United States.
authors.forename: Veena M
authors.initials: VM
authors.lastname: Bhopale
authors.affiliation: Department of Emergency Medicine, University of Maryland, Baltimore, MD 21201, United States.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Emergency Medicine, University of Maryland, Baltimore, MD 21201, United States.
authors.forename: Kinjal
authors.initials: K
authors.lastname: Sethuraman
authors.affiliation: Department of Emergency Medicine, University of Maryland, Baltimore, MD 21201, United States. Electronic address: sthom@smail.umaryland.edu.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Thom
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects; D000199:Actins / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000818:Animals; D001128:Argon / Q000494:pharmacology*; D001792:Blood Platelets / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000187:drug effects*; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006371:Helium / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D000074662:NADPH Oxidase 2 / Q000172:deficiency / Q000235:genetics; D052247:Nitric Oxide Synthase Type II / Q000172:deficiency / Q000235:genetics; D009584:Nitrogen / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D026082:Singlet Oxygen / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D000199:Actins; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; C107953:RAC1 protein, human; D000098662:Vasodilator-Stimulated Phosphoprotein; D026082:Singlet Oxygen; D006371:Helium; D001128:Argon; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D020830:rac1 GTP-Binding Protein; D009584:Nitrogen
keywords: Filamentous actin; Focal adhesion kinase; NADPH oxidase; Reactive nitrogen species; S-nitrosylation; Singlet oxygen