Abstract Objective To study the effect of uncoupling protein 2 (UCP2)-siRNA on the inflammatory response of rat cardiomyocytes (H9C2) induced by septic serum and to investigate the possible role of UCP2 in the development of septic cardiomyopathy. Methods Serum samples were separately collected from normal rats and septic rats. Cultured rat cardiac cells (H9C2) were randomly divided into blank control, normal serum, 10% septic serum, UCP2-siRNA+10% septic serum and negative siRNA+10% septic serum groups. Stimulation with 10% septic serum was performed for 12 hours in relevant groups. The mRNA expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) was measured by RT-PCR. The expression of phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) and nuclear factor-kappa B (NF-κB) was measured by Western blot. Results The expression levels of p-p38 and NF-κB in the UCP2-siRNA+10% septic serum group were significantly higher than in the 10% septic serum group (PPConclusions UCP2 plays a regulatory role in the activation of p38 MAPK and NF-κB and the expression of downstream inflammatory mediators in H9C2 cells stimulated with septic serum.
CHEN Zhi-Jiang,SONG Yuan-Bin,WANG Hui-Li et al. Effect of UCP2-siRNA on inflammatory response of cardiomyocytes induced by septic serum[J]. CJCP, 2014, 16(8): 851-855.
CHEN Zhi-Jiang,SONG Yuan-Bin,WANG Hui-Li et al. Effect of UCP2-siRNA on inflammatory response of cardiomyocytes induced by septic serum[J]. CJCP, 2014, 16(8): 851-855.
Donadelli M, Dando I, Fiorini C, et al. UCP2, a mitochondrial protein regulated at multiple levels[J]. Cell Mol Life Sci, 2014, 71(7): 1171-1190.
[2]
Azzu V, Jastroch M, Divakaruni AS, et al. The regulation and turnover of mitochondrial uncoupling proteins[J]. Biochim Biophys Acta, 2010, 1797(6-7): 785-791.
[3]
Emre Y, Nübel T. Uncoupling protein UCP2: When mitochondrial activity meets immunity[J]. FEBS Letters, 2010, 584(8): 1437-1442.
[4]
Fink MP, Heard SO. Laboratory models of sepsis and septic shock[J]. J Surg Res, 1990, 49(2): 186-196.
[5]
Vieillard-Baron A. Septic cardiomyopathy[J]. Annals of Intensive Care, 2011, 1(1): 6.
[6]
Flynn A, Chokkalingam Mani B, Mather PJ. Sepsis-induced cardiomyopathy: a review of pathophysiologic mechanisms[J]. Heart Fail Rev, 2010, 5(6): 605-611.
[7]
Shimaoka M, Park EJ. Advances in understanding sepsis[J]. Eur J Anaesthesiol Suppl, 2008, 42(25): 146-153.
Zhang T, Feng Q. Nitric oxide and calcium signaling regulate myocardial tumor necrosis factor-a expression and cardiac function in sepsis[J]. Can J Physiol Pharmacol, 2010, 88(2): 92- 104.
[11]
Yang M, Wu J, Martin CM, et al. Important role of p38 MAP kinaseNF-kB signaling pathway in the sepsis-induced conversion of cardiac myocytes to a proinflammatory phenotype[J]. Am J Physiol Heart Circ Physiol, 2008, 294(2): H994-H1001.
[12]
Yushi B, Hiroki O, Xu B, et al. Persistent Nuclear Factor-kB Activation in Ucp2-- Mice Leads to Enhanced Nitric Oxide and Inflammatory Cytokine Production[J]. J Biol Chem, 2005, 13, 280(19): 19062-19069.
[13]
Chul SY, Jae MY, Jwa JK, et al. Small heterodimer partnertargeting therapy inhibits systemic inflammatory responses through mitochondrial uncoupling protein 2[J]. PLoS ONE, 2013, 8(5): e63435.
