title: Anti-apoptotic role of sonic hedgehog on blood platelets.
abstract: Sonic hedgehog (Shh) is an essential morphogen involved in vertebrate organogenesis. Perturbation of Hh signaling is associated with pathological consequences like tumor formation and chronic lung fibrosis. Platelets are highly sensitive circulating blood cells responsible for hemostasis, while hyperactivity of these cells lead to morbidities like ischemic heart diseases and stroke. Despite being terminally differentiated cells with life span of 10-12 days, platelets have recently been shown to respond to Wnt ligand, another developmental signal similar to Shh. In this study, we demonstrate that components of Shh signaling, Patched and Gli3, are expressed in human platelets consistent with existence of functional Hedgehog signaling in these cells. Shh had potent inhibitory effect on platelet apoptosis induced by ABT-737 or thrombin through attenuation of caspase-3 activity. The Shh-mediated pathway may thus represent a novel endogenous mechanism for regulating platelet activity and life span.
authors.affiliation: Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India.
authors.forename: Sharda
authors.initials: S
authors.lastname: Kumari
authors.affiliation: Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India.
authors.forename: Susheel N
authors.initials: SN
authors.lastname: Chaurasia
authors.affiliation: Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India.
authors.forename: Kailash
authors.initials: K
authors.lastname: Kumar
authors.affiliation: Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India. Electronic address: ddash.biochem@gmail.com.
authors.forename: Debabrata
authors.initials: D
authors.lastname: Dash
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001713:Biphenyl Compounds / Q000008:administration & dosage; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D009596:Nitrophenols / Q000008:administration & dosage; D010879:Piperazines / Q000008:administration & dosage; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013449:Sulfonamides / Q000008:administration & dosage
chemical_list: C501332:ABT-737; D001713:Biphenyl Compounds; D053823:Hedgehog Proteins; D009596:Nitrophenols; D010879:Piperazines; D017382:Reactive Oxygen Species; C509239:SHH protein, human; D013449:Sulfonamides; D053148:Caspase 3
keywords: Apoptosis; Caspase; Hedgehog signaling; Platelet