Journal of Shanghai University >
Macrophage migration inhibitory factor deficiency aggravates cardiac hypertrophy induced by phenylephrine in mice
Received date: 2016-04-19
Online published: 2016-06-30
To investigate the effect of macrophage migration inhibitory factor (MIF) deficiency on the cardiac hypertrophy induced by hypodermic injection of phenylephrine (PE) in mice. A mouse model of cardiac hypertrophy induced by hypodermic injection of PE was established based on MIF-knockout (MIF-KO) mouse and the wide type control (WT) mouse. The left ventricular (LV) structure and function variables were assessed by transthoracic echocardiography. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay was performed to detect cardiomyocyte apoptosis. Expressions of SOD1, SOD2 and Trx2 were determined by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western Blot assay, respectively. ①A mouse model of cardiac hypertrophy was achieved, induced by hypodermic injection of 20 mg/(kg·d) PE for 3 d. Compared with WT mice, PE injection induced more severe cardiac hypertrophy in MIF-KO mice. ②TUNEL assay revealed that the level of PE injection-induced cardiomyocte apoptosis in the myocardium of MIF-KO mouse was higher than that in WT mice. ③Expressions of SOD1 and Trx2 were significantly decreased in the myocardium of MIF-KO mice after PE injection, and reduction of Trx2 protein in myocardium of MIF-KO mice was more than that in WT mouse. MIF deficiency attenuates the expressions of SOD1 and Trx2, contributing to the aggravation of cardiomyocyte apoptosis and cardiac hypertrophy induced by hypodermic injection of PE in mice.
XIAO Zhen, ZHU Jiening, TANG Chunmei, LIN Qiuxiong, HU Zhiqin, ZHANG Zhuo, FU Yongheng, ZHANG Mengzhen, SHAN Zhixin . Macrophage migration inhibitory factor deficiency aggravates cardiac hypertrophy induced by phenylephrine in mice[J]. Journal of Shanghai University, 2016 , 22(3) : 336 -343 . DOI: 10.3969/j.issn.1007-2861.2016.03.011
[1] Grieb G, Merk M, Bernhagen J, et al. Macrophage migration inhibitory factor (MIF): a promising biomarker [J]. Drug News Perspect, 2010, 23: 257-264.
[2] Xu X, Hua Y, Nair S, et al. Macrophage migration inhibitory factor deletion exacerbates pressure overload-induced cardiac hypertrophy through mitigating autophagy [J]. Hypertension, 2014, 63: 490-499.
[3] Koga K, Kenessey A, Ojamaa K. Macrophage migration inhibitory factor antagonizes pressure overload-induced cardiac hypertrophy [J]. Am J Physiol Heart Circ Physiol, 2013, 304: H282-H293.
[4] Slawson S E, Roman B B, Williams D S, et al. Cardiac MRI of the normal and hypertrophied mouse heart [J]. Magn Reson Med, 1998, 39: 980-987.
[5] Kleemann R, Kapurniotu A, Frank R W, et al. Disulfide analysis reveals a role for macrophage migration inhibitory factor (MIF) as thiol-protein oxidoreductase [J]. J Mol Biol,
1998, 280: 85-102.
[6] Thiele M, Bernhagen J. Link between macrophage migration inhibitory factor and cellular redox regulation [J]. Antioxid Redox Signal, 2005, 7: 1234-1238.
[7] Luedike P, Hendgen-Cotta U B, Sobierajski J, et al. Cardioprotection through Snitros(yl)ation of macrophage migration inhibitory factor [J]. Circulation, 2012, 125: 1880-1889.
[8] Su H, Li J, Menon S, et al. Perturbation of cullin deneddylation via conditional Csn8 ablation impairs the ubiquitin-proteasome system and causes cardiomyocyte necrosis and dilated cardiomyopathy in mice [J]. Circ Res, 2011, 108: 40-50.
[9] Koga K, Kenessey A, Powell S R, et al. Macrophage migration inhibitory factor provides cardioprotection during ischemia/reperfusion by reducing oxidative stress [J]. Antioxid Redox
Signal, 2011, 14: 1191-1202.
[10] Miller E J, Li J, Leng L, et al. Macrophage migration inhibitory factor stimulates AMPactivated protein kinase in the ischaemic heart [J]. Nature, 2008, 451: 578-582.
[11] Qi D, Hu X,Wu X, et al. Cardiac macrophage migration inhibitory factor inhibits JNK pathway activation and injury during ischemia/reperfusion [J]. J Clin Invest, 2009, 119: 3807-3816.
[12] Zhang T T, Takimoto K, Stewart A F, et al. Independent regulation of cardiac Kv4.3 potassium channel expression by angiotensin Ⅱ and phenylephrine [J]. Circ Res, 2001, 88: 476-482.
[13] Maulik S K, Kumar S. Oxidative stress and cardiac hypertrophy: a review [J]. Toxicol Mech Methods, 2012, 22: 359-366.
[14] Sag C M, Santos C X, Shah A M. Redox regulation of cardiac hypertrophy [J]. J Mol Cell Cardiol, 2014, 73: 103-111.
/
| 〈 |
|
〉 |
