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: F Rao, C Y Deng, Q H Zhang, Y M Xue, D Z Xiao, S J Kuang, Q X Lin, Z X Shan, X Y Liu, J N Zhu, X Y Yu, S L Wu
• Journal: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas (Braz J Med Biol Res) Vol. 46 Issue 9 Pg. 746-51 (Sep 2013) ISSN: 1414-431X [Electronic] Brazil
• PMID: 24036910 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Macrophage Migration-Inhibitory Factors
• Oxidants
• Protein Kinase Inhibitors
• Angiotensin II
• Hydrogen Peroxide
• src-Family Kinases
• Protein Kinase C
• Intramolecular Oxidoreductases
• Mif protein, mouse

Topics

• Angiotensin II (metabolism)
• Animals
• Blotting, Western
• Cell Line
• Hydrogen Peroxide (pharmacology)
• Immunohistochemistry
• Intramolecular Oxidoreductases (drug effects, genetics)
• Macrophage Migration-Inhibitory Factors (drug effects, genetics)
• Mice
• Microscopy, Confocal
• Myocytes, Cardiac (metabolism)
• Oxidants (pharmacology)
• Oxidative Stress (physiology)
• Protein Kinase C (metabolism)
• Protein Kinase Inhibitors (pharmacology)
• Real-Time Polymerase Chain Reaction
• Renin-Angiotensin System (physiology)
• src-Family Kinases (metabolism)