title: Involvement of Src tyrosine kinase and protein kinase C in the expression of macrophage migration inhibitory factor induced by H2O2 in HL-1 mouse cardiac muscle cells.
abstract: Macrophage migration inhibitory factor (MIF), a pleiotropic cytokine, plays an important role in the pathogenesis of atrial fibrillation; however, the upstream regulation of MIF in atrial myocytes remains unclear. In the present study, we investigated whether and how MIF is regulated in response to the renin-angiotensin system and oxidative stress in atrium myocytes (HL-1 cells). MIF protein and mRNA levels in HL-1 cells were assayed using immunofluorescence, real-time PCR, and Western blot. The result indicated that MIF was expressed in the cytoplasm of HL-1 cells. Hydrogen peroxide (H2O2), but not angiotensin II, stimulated MIF expression in HL-1 cells. H2O2-induced MIF protein and gene levels increased in a dose-dependent manner and were completely abolished in the presence of catalase. H2O2-induced MIF production was completely inhibited by tyrosine kinase inhibitors genistein and PP1, as well as by protein kinase C (PKC) inhibitor GF109203X, suggesting that redox-sensitive MIF production is mediated through tyrosine kinase and PKC-dependent mechanisms in HL-1 cells. These results suggest that MIF is upregulated by HL-1 cells in response to redox stress, probably by the activation of Src and PKC.
authors.affiliation: Guangdong Academy of Medical Sciences, Guangdong Cardiovascular Institute, Guangdong General Hospital, Department of Cardiology, Guangzhou, China.
authors.forename: F
authors.initials: F
authors.lastname: Rao
authors.forename: C Y
authors.initials: CY
authors.lastname: Deng
authors.forename: Q H
authors.initials: QH
authors.lastname: Zhang
authors.forename: Y M
authors.initials: YM
authors.lastname: Xue
authors.forename: D Z
authors.initials: DZ
authors.lastname: Xiao
authors.forename: S J
authors.initials: SJ
authors.lastname: Kuang
authors.forename: Q X
authors.initials: QX
authors.lastname: Lin
authors.forename: Z X
authors.initials: ZX
authors.lastname: Shan
authors.forename: X Y
authors.initials: XY
authors.lastname: Liu
authors.forename: J N
authors.initials: JN
authors.lastname: Zhu
authors.forename: X Y
authors.initials: XY
authors.lastname: Yu
authors.forename: S L
authors.initials: SL
authors.lastname: Wu
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007150:Immunohistochemistry; D019746:Intramolecular Oxidoreductases / Q000187:drug effects* / Q000235:genetics; D008263:Macrophage Migration-Inhibitory Factors / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D018613:Microscopy, Confocal; D032383:Myocytes, Cardiac / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D012084:Renin-Angiotensin System / Q000502:physiology; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D016877:Oxidants; D047428:Protein Kinase Inhibitors; D000804:Angiotensin II; D006861:Hydrogen Peroxide; D019061:src-Family Kinases; D011493:Protein Kinase C; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse
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