title: Role of JAK-STAT pathway in reducing cardiomyocytes hypoxia/reoxygenation injury induced by S1P postconditioning.
abstract: This experiment was designed to explore the protection of sphingosine1-phosphate (S1P) postconditioning on rat myocardial cells injured by hypoxia/reoxygenation acting via the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signal pathway. The data showed that S1P could significantly increase cell viability, lower the rate of apoptosis, decrease the content of lactate dehydrogenase (LDH) and caspase3 activity in the culture medium, increase the activity of total superoxide dismutase (T-SOD) and manganese superoxide dismutase (Mn-SOD), reduce the loss of mitochondrial membrane potential and the fluorescence intensity of intracellular calcium, as well as increase the phosphorylation of JAK2 and STAT3 in comparison with the H/R group. When the JAK inhibitor AG490 or the STAT inhibitor stattic were added, the effects of S1P were inhibited. Our date shows that S1P protects H9c2 cells from hypoxia/reoxygenation injury and that the protection by S1P was inhibited by AG490 and stattic. Therefore S1P protects H9c2 cells against hypoxia/reoxygenation injury via the JAK-STAT pathway.
authors.affiliation: Department of Pharmacology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Dongfei
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Tianjin First Center Hospital, Tianjin 300192, China.
authors.forename: Lizhi
authors.initials: L
authors.lastname: Zhang
authors.affiliation: College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China.
authors.forename: Fangyu
authors.initials: F
authors.lastname: Ye
authors.affiliation: Department of Pharmacology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Tianjin Medical University, Tianjin 300070, China. Electronic address: wenke@tijmu.edu.cn.
authors.forename: Ke
authors.initials: K
authors.lastname: Wen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D003499:Cyclic S-Oxides / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D057775:Ischemic Postconditioning / Q000379:methods*; D053612:Janus Kinases / Q000378:metabolism*; D008246:Lysophospholipids / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010100:Oxygen / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D003499:Cyclic S-Oxides; D008246:Lysophospholipids; D010750:Phosphoproteins; D050791:STAT Transcription Factors; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; C517409:stattic; C060506:sphingosine 1-phosphate; D013482:Superoxide Dismutase; D053612:Janus Kinases; D053148:Caspase 3; D013110:Sphingosine; D010100:Oxygen; D002118:Calcium
keywords: AG490; AG490 (PubChem CID: 5328779); DMSO (PubChem CID: 679); FITC (PubChem CID: 18730); Fluo-3 AM (PubChem CID: 104978); H9c2; JAK-STAT pathway; JC-1 (PubChem CID: 5492929); S1P; Stattic; methyl thiazolyl tetrazolium (PubChem CID: 64965); sphingosine-1-phosphate (PubChem CID: 5283560); stattic (PubChem CID: 2779853)