Involvement of Src tyrosine kinase and protein kinase C in the expression of macrophage migration inhibitory factor induced by H sub(2)O sub(2) in HL-1 mouse cardiac muscle cells

• Published in: Brazilian journal of medical and biological research Vol. 46; no. 9; pp. 746 - 751
• Main Authors: Rao, F, Deng, C Y, Zhang, Q H, Xue, Y M, Xiao, D Z, Kuang, S J, Lin, Q X, Shan, Z X, Liu, X Y, Zhu, J N, Yu, X Y, Wu, S L
• Format: Journal Article
• Language: English
• Published: 01-09-2013
• ISSN: 0100-879X; 1414-431X
• DOI: 10.1590/1414-431X20132936

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 (H sub(2)O sub(2)), but not angiotensin II, stimulated MIF expression in HL-1 cells. H sub(2)O sub(2)-induced MIF protein and gene levels increased in a dose-dependent manner and were completely abolished in the presence of catalase. H sub(2)O sub(2)-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.