Regulation of platelet activation and thrombus formation by reactive oxygen species
Jianlin Qiao,
Jane F. Arthur,
Elizabeth E. Gardiner,
Robert K. Andrews,
Lingyu Zeng,
Kailin Xu
Affiliations
Jianlin Qiao
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China; Key Laboratory of Bone Marrow Stem Cell, Xuzhou, Jiangsu Province, China; Corresponding author at: Blood Diseases Institute, Xuzhou Medical University, 84 West Huaihai Road, Quanshan District, Xuzhou 221002, China.
Jane F. Arthur
Australian Centre for Blood Diseases, Monash University, Melbourne, Australia
Elizabeth E. Gardiner
ACRF Department of Cancer Biology and Therapeutics, John Curtin School of Medical Research, Australian National University, Canberra, Australia
Robert K. Andrews
Australian Centre for Blood Diseases, Monash University, Melbourne, Australia
Lingyu Zeng
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China; Key Laboratory of Bone Marrow Stem Cell, Xuzhou, Jiangsu Province, China
Kailin Xu
Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China; Key Laboratory of Bone Marrow Stem Cell, Xuzhou, Jiangsu Province, China; Corresponding author at:Â Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Quanshan District, Xuzhou 221002, China.
Reactive oxygen species (ROS) are generated within activated platelets and play an important role in regulating platelet responses to collagen and collagen-mediated thrombus formation. As a major collagen receptor, platelet-specific glycoprotein (GP)VI is a member of the immunoglobulin (Ig) superfamily, with two extracellular Ig domains, a mucin domain, a transmembrane domain and a cytoplasmic tail. GPVI forms a functional complex with the Fc receptor γ-chain (FcRγ) that, following receptor dimerization, signals via an intracellular immunoreceptor tyrosine-based activation motif (ITAM), leading to rapid activation of Src family kinase signaling pathways. Our previous studies demonstrated that an unpaired thiol in the cytoplasmic tail of GPVI undergoes rapid oxidation to form GPVI homodimers in response to ligand binding, indicating an oxidative submembranous environment in platelets after GPVI stimulation. Using a redox-sensitive fluorescent dye (H2DCF-DA) in a flow cytometric assay to measure changes in intracellular ROS, we showed generation of ROS downstream of GPVI consists of two distinct phases: an initial Syk-independent burst followed by additional Syk-dependent generation. In this review, we will discuss recent findings on the regulation of platelet function by ROS, focusing on GPVI-dependent platelet activation and thrombus formation. Keywords: Platelet activation, Thrombus formation, GPVI, ROS
