Impact of proteasome inhibitor MG‑132 on expression of NF‑κB, IL‑1β and histological remodeling after myocardial infarction

Wu,Xinhua; Chen,Zhangrong; Yang,Ying; Dong,Yu; Liu,Hong; Kuang,Shiquan; Luo,Kailiang

doi:10.3892/etm.2018.6308

Impact of proteasome inhibitor MG‑132 on expression of NF‑κB, IL‑1β and histological remodeling after myocardial infarction

Authors:
- Xinhua Wu
- Zhangrong Chen
- Ying Yang
- Yu Dong
- Hong Liu
- Shiquan Kuang
- Kailiang Luo
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Affiliations: Department of Cardiology, The First Affiliated Hospital of Dali University, Dali, Yunnan 671000, P.R. China, Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 404100, P.R. China
Published online on: June 13, 2018 https://doi.org/10.3892/etm.2018.6308
Pages: 1365-1372

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Abstract

The aim of the present study was to investigate the impact of carbobenzoxy‑Leu‑Leu‑leucinal (MG‑132) on myocardial remodeling in rats with myocardial infarction (MI) and investigate the possible underlying mechanisms. The rat model of MI was established, followed by administration of MG‑132 (MG group), pyrrolidine dithiocarbamic acid (PDTC group) or normal saline (MI group) for 28 days. The expression of nuclear factor‑κB (NF‑κB) p65, interleukin 1β (IL‑1β) and matrix metalloproteinase 2 (MMP‑2), as well as the total volume of collagen and the ratio of type I/III collagen were then detected. Total collagen, including type I and III collagen, and the ratio of type I/III collagen were significantly increased in MI rats compared with those in the sham group (P<0.01), while it was significantly decreased in the PDTC and MG groups compared with that in the MI group (P<0.01). A similar trend was identified for the expression of NF‑κB, IL‑1β and MMP‑2, which was significantly increased in the MI group compared with that in the sham group (P<0.01), while it was significantly decreased in the MG and PDTC groups compared with that in the MI group (P<0.01). In conclusion, MG‑132 was demonstrated to improve post‑MI tissue remodeling, and the mechanism may be associated with the inhibition of NF‑κB activation and the downregulation of inflammatory cytokines, such as IL‑1β.

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1	Seropian IM, Toldo S, Van Tassell BW and Abbate A: Anti-inflammatory strategies for ventricular remodeling following ST-segment elevation acute myocardial infarction. J Am Coll Cardiol. 63:1593–1603. 2014. View Article : Google Scholar : PubMed/NCBI
2	Shioi T, Matsumori A, Kihara Y, Inoko M, Ono K, Iwanaga Y, Yamada T, Iwasaki A, Matsushima K and Sasayama S: Increased expression of interleukin-1 beta and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in the hypertrophied and failing heart with pressure overload. Circ Res. 81:664–671. 1997. View Article : Google Scholar : PubMed/NCBI
3	Zarrouk-Mahjoub S, Zaghdoudi M, Amira Z, Chebi H, Khabouchi N, Finsterer J, Mechmeche R and Ghazouani E: Pro- and anti-inflammatory cytokines in post-infarction left ventricular remodeling. Int J Cardiol. 221:632–636. 2016. View Article : Google Scholar : PubMed/NCBI
4	Wang S, Kotamraju S, Konorev E, Kalivendi S, Joseph J and Kalyanaraman B: Activation of nuclear factor-kappaB during doxorubicin-induced apoptosis in endothelial cells and myocytes is pro-apoptotic: The role of hydrogen peroxide. Biochem J. 367:729–740. 2002. View Article : Google Scholar : PubMed/NCBI
5	Sun B, Xia Q and Gao Z: Total flavones of choerospondias axillaris attenuate cardiac dysfunction and myocardial interstitial fibrosis by modulating NF-kB signaling pathway. Cardiovasc Toxicol. 15:283–289. 2015. View Article : Google Scholar : PubMed/NCBI
6	Xiao C and Ghosh S: NF-kappaB, an evolutionarily conserved mediator of immune and inflammatory responses. Adv Exp Med Biol. 560:41–45. 2005. View Article : Google Scholar : PubMed/NCBI
7	Zandi E and Karin M: Bridging the gap: Composition, regulation, and physiological function of the IkappaB kinase complex. Mol Cell Biol. 19:4547–4551. 1999. View Article : Google Scholar : PubMed/NCBI
8	Tanner H, Mohacsi P, Fuller-Bicer GA, Rieben R, Meier B, Hess O and Hullin R: Cytokine activation and disease progression in patients with stable moderate chronic heart failure. J Heart Lung Transplant. 26:622–629. 2007. View Article : Google Scholar : PubMed/NCBI
9	Elliott PJ, Zollner TM and Boehncke WH: Proteasome inhibition: A new anti-inflammatory strategy. J Mol Med (Berl). 81:235–245. 2003. View Article : Google Scholar : PubMed/NCBI
10	Santos DG, Resende MF, Mill JG, Mansur AJ, Krieger JE and Pereira AC: Nuclear Factor (NF) kappaB polymorphism is associated with heart function in patients with heart failure. BMC Med Genet. 11:892010. View Article : Google Scholar : PubMed/NCBI
11	Chen FT, Yang CM and Yang CH: The protective effects of the proteasome inhibitor bortezomib (velcade) on ischemia-reperfusion injury in the rat retina. PLoS One. 8:e642622013. View Article : Google Scholar : PubMed/NCBI
12	Ma Y, Chen B, Liu D, Yang Y, Xiong Z, Zeng J and Dong Y: MG132 treatment attenuates cardiac remodeling and dysfunction following aortic banding in rats via the NF-κB/TGFβ1 pathway. Biochem Pharmacol. 81:1228–1236. 2011. View Article : Google Scholar : PubMed/NCBI
13	Zimmermann M: Ethical guidelines for investigations of experimental pain in conscious animals. Pain. 16:109–110. 1983. View Article : Google Scholar : PubMed/NCBI
14	Jin JL, Lv RG, Guo J, Liu XH, Liang YW, Wei JR and Wang L: Improvement of left ventricular remodelling by inhibition of NF-κB in a rat model of myocardial infarction. Heart Lung Circ. 25:1007–1012. 2016. View Article : Google Scholar : PubMed/NCBI
15	Chen ZR, Wu XH, Luo KL, He Q and Xiang YL: Proteasome inhibitor MG-132 improves myocadial hypertrophy after myocardial infarction in rats. Basic Clin Med. 32:1326–1331. 2012.(In Chinese).
16	Snyder JG, Prewitt R, Campsen J and Britt LD: PDTC and Mg132, inhibitors of NF-kappaB, block endotoxin induced vasodilation of isolated rat skeletal muscle arterioles. Shock. 17:304–307. 2002. View Article : Google Scholar : PubMed/NCBI
17	Lattouf R, Younes R, Lutomski D, Naaman N, Godeau G, Senni K and Changotade S: Picrosirius red staining: A useful tool to appraise collagen networks in normal and pathological tissues. J Histochem Cytochem. 62:751–758. 2014. View Article : Google Scholar : PubMed/NCBI
18	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
19	Huang W, Li SN, Huang S and Xu B: Inhibitor of ubiquitin proteasome system suppress Calcineurin-dependent cardiomyocyte hypertrophy. Chin J Arteriosclerosis. 22:774–778. 2014.(In Chinese).
20	Meiners S, Hocher B, Weller A, Laule M, Stangl V, Guenther C, Godes M, Mrozikiewicz A, Baumann G and Stangl K: Downregulation of matrix metalloproteinases and collagens and suppression of cardiac fibrosis by inhibition of the proteasome. Hypertension. 44:471–477. 2004. View Article : Google Scholar : PubMed/NCBI
21	Wang Y, Suo F, Liu J, Hu H, Xue M, Cheng W, Xuan Y and Yan S: Myocardial infarction induces sympathetic hyperinnervation via a nuclear factor-κB-dependent pathway in rabbit hearts. Neurosci Lett. 535:128–133. 2013. View Article : Google Scholar : PubMed/NCBI
22	Li B, Liao YH, Cheng X, Ge H, Guo H and Wang M: Effects of carvedilol on cardiac cytokines expression and remodeling in rat with acute myocardial infarction. Int J Cardiol. 111:247–255. 2006. View Article : Google Scholar : PubMed/NCBI
23	Wójcik S, Spodnik JH, Spodnik E, Dziewiątkowski J and Moryś J: Nigrostriatal pathway degeneration in rats after intraperitoneal administration of proteasome inhibitor MG-132. Folia Neuropathol. 52:41–55. 2014. View Article : Google Scholar : PubMed/NCBI
24	Wang Y, Sun W, Du B, Miao X, Bai Y, Xin Y, Tan Y, Cui W, Liu B, Cui T, et al: Therapeutic effect of MG-132 on diabetic cardiomyopathy is associated with its suppression of proteasomal activities: Roles of Nrf2 and NF-κB. Am J Physiol Heart Circ Physiol. 304:H567–H578. 2013. View Article : Google Scholar : PubMed/NCBI
25	Chen SF, Chen HY, Liu XB, Zhang YX, Liu W, Wang WH, Zhang B and Wang LX: Apoptotic effect of MG-132 on human tongue squamous cell carcinoma. Biomed Pharmacother. 65:322–327. 2011. View Article : Google Scholar : PubMed/NCBI