Journal of Shanghai University >
Effectiveness of activation of sigma-1 receptor on reducing myocardium injury in ischemia reperfusion
Received date: 2018-06-22
Online published: 2018-12-24
[Objective] This paper attempts to investigate whether sigma-1 receptor (Sig1R) activation attenuate myocardial ischemia reperfusion injury (MIRI) and whether Sig1R inhibition exacerbates MIRI in mice model. [Methods] C57BL/6 mice are injected via tail vein with BD1047 (Sig1R inhibitor), SA4503 (Sig1R activator) or saline 3 days before MIRI surgery. Then, double-staining technique and western blot analysis are performed on myocardium tissue. [Results] Mice that have received BD1047 pretreatment demonstrate a significant increase in the myocardial infarction size after I/R compared with control group ($P\!\!<$0.05), and a significantly increased expression of Bax and Caspases-3 proteins and a significantly reduced expression of Bcl-2 protein compared with sham control, MIRI control and sham BD1047 groups ($P\!<$0.05). Mice that have received SA4503 pretreatment demonstrate a significant reduction in myocardial infarction size after I/R compared with control group ($P\!<$0.05), and a significantly reduced expression of Bax and cleaved Caspases-3 proteins and a significantly increased expression of Bcl-2 protein compared with sham control, MIRI control and sham SA4503 groups ($P\!<$0.05). [Conclusions] SA4503 protects MIRI and reduces myocardial infarction whereas BD1047 deteriorates MIRI and augment myocardial infarction, and these effects may be achieved through activation or inhibition of Sig1R.
LIAO Xiaoping, YU Pujiao, XU Jiahong . Effectiveness of activation of sigma-1 receptor on reducing myocardium injury in ischemia reperfusion[J]. Journal of Shanghai University, 2018 , 24(6) : 853 -860 . DOI: 10.12066/j.issn.1007-2861.2096
| [1] | Yellon D M, Hausenloy D J. Myocardial reperfusion injury[J]. N Engl J Med, 2007,357:1121-1135. |
| [2] | Hausenloy D J, Yellon D M. Targeting myocardial reperfusion injury: the search continues[J]. N Engl J Med, 2015,373:1073-1075. |
| [3] | Hausenloy D J, Yellon D M. Myocardial ischemia-reperfusion injury: a neglected therapeutic target[J]. J Clin Invest, 2013,123:92-100. |
| [4] | Ibá?ez B, Heusch G, Ovize M, et al. Evolving therapies for myocardial ischemia/reperfusion injury[J]. J Am Coll Cardiol, 2015,65:1454-1471. |
| [5] | Lejay A, Fang F, John R, et al. Ischemia reperfusion injury, ischemic conditioning and diabetes mellitus[J]. Journal of Molecular and Cellular Cardiology, 2016,91:11-22. |
| [6] | Hayashi T, Su T P. Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca2+ signaling and cell survival [J]. Cell, 2007,131:596-610. |
| [7] | Su T P, Hayashi T, Maurice T, et al. The sigma-1 receptor chaperone as an inter-organelle signaling modulator[J]. Trends Pharmacol Sci, 2010,31:557-566. |
| [8] | Fujimoto M, Hayashi T, Urfer R, et al. Sigma-1 receptor chaperones regulate the secretion of brain-derived neurotrophic factor[J]. Synapse, 2012,66:630-639. |
| [9] | Meunier J, Hayashi T. Sigma-1 receptors regulate Bcl-2 expression by reactive oxygen species-dependent transcriptional regulation of NF$\kappa$B[J]. J Pharmacol Exp Ther, 2010,332:388-397. |
| [10] | Tsai S Y, Hayashi T, Mori T, et al. Sigma-1 receptor chaperones and diseases[J]. Cent Nerv Syst Agents Med Chem, 2009,9:184-189. |
| [11] | Klouz A, Sa?d D B, Ferchichi H, et al. Protection of cellular and mitochondrial functions against liver ischemia by $N$-benzyl-$N$'-(2-hydroxy-3,4-dimethoxybenzyl)-piperazine (BHDP), a sigma1 ligand[J]. Eur J Pharmacol, 2008,578(2/3):292-299. |
| [12] | Hosszu A, Antal Z, Lenart L, et al. $\sigma $1-receptor agonism protects against renal ischemia-reperfusion injury[J]. J Am Soc Nephrol, 2017,28(1):152-165. |
| [13] | Bucolo C, Drago F. Neuroactive steroids protect retinal tissue through $\sigma $1 receptors[J]. Basic Clin Pharmacol Toxicol, 2007,100:214-216. |
| [14] | Shen Y C, Wang Y H, Chou Y C, et al. Dimemorfan protects rats against ischemic stroke through activation of sigma-1 receptor-mediated mechanisms by decreasing glutamate accumulation[J]. J Neurochem, 2008,104:558-572. |
| [15] | Tagashira H, Zhang C, Lu Y M, et al. Stimulation of $\sigma $1-receptor restores abnormal mitochondrial Ca2+ mobilization and ATP production following cardiac hypertrophy [J]. Biochim Biophys Acta, 2013,1830:3082-3094. |
| [16] | Tagashira H, Bhuiyan M S, Shioda N, et al. Fluvoxamine rescues mitochondrial Ca2+ transport and ATP production through $\sigma $1-receptor in hypertrophic cardiomyocytes [J]. Life Sci, 2014,95:89-100. |
| [17] | Bhuiyan M S, Fukunaga K. Stimulation of sigma-1 receptor signaling by dehydroepiandrosterone ameliorates pressure overload-induced hypertrophy and dysfunctions in ovariectomized rats[J]. Expert Opin Ther Targets, 2009,13:1253-1265. |
| [18] | Bhuiyan M S, Tagashira H, Fukunaga K. Dehydroepiandrosterone mediated stimulation of sigma-1 receptor activates Akt-eNOS signaling in the thoracic aorta of ovariectomized rats with abdominal aortic banding[J]. Cardiovasc Ther, 2010,29:219-230. |
| [19] | Bhuiyan M S, Tagashira H, Fukunaga K. Sigma-1 receptor stimulation with fluvoxamine activates Akt-eNOS signaling in the thoracic aorta of ovariectomized rats with abdominal aortic banding[J]. Eur J Pharmacol, 2011,650:621-628. |
| [20] | Ito K, Hirooka Y, Matsukawa R, et al. Decreased brain sigma-1 receptor contributes to the relationship between heart failure and depression[J]. Cardiovas Res, 2012,93:33-40. |
| [21] | Dumont E A, Hofstra L, Van Heerde W L, et al. Cardiomyocyte death induced by myocardial ischemia and reperfusion: measurement with recombinant human annexin-Ⅴ in a mouse model[J]. Circulation, 2000,102:1564-1568. |
| [22] | Dumont E A, Reutelingsperger C P, Smits J F, et al. Real-time imaging of apoptotic cell-membrane changes at the single-cell level in the beating murine heart[J]. Nature Medicine, 2001,7(12):1352-1355. |
| [23] | Whelan R S, Kaplinskiy V, Kitsis R N. Cell death in the pathogenesis of heart disease: mechanisms and significance[J]. Annu Rev Physiol, 2010,72:19-44. |
| [24] | Hausenloy D J, Yellon D M. The mitochondrial permeability transition pore: its fundamental role in mediating cell death during ischaemia and reperfusion[J]. J Mol Cell Cardiol, 2003,35:339-341. |
| [25] | Ong S B, Samangouei P, Kalkhoran S B, et al. The mitochondrial permeability transition pore and its role in myocardial ischemia reperfusion injury[J]. J Mol Cell Cardiol, 2015,78:23-34. |
| [26] | Fliss H, Gattinger D. Apoptosis in ischemic and reperfused rat myocardium[J]. Circ Res, 1996,79:949-956. |
| [27] | Di Lisa F, Canton M, Menabo R, et al. Mitochondria and reperfusion injury: the role of permeability transition[J]. Basic Res Cardiol, 2003,98:235-241. |
| [28] | Halestrap A P, Richardson A P. The mitochondrial permeability transition: a current perspective on its identity and role in ischaemia/reperfusion injury[J]. J Mol Cell Cardiol, 2015,78:129-141. |
| [29] | Eltzschig H K, Eckle T. Ischemia and reperfusion: from mechanism to translation[J]. Nat Med, 2011,17:1391-1401. |
| [30] | Shimazawa M, Sugitani S, Inoue Y, et al. Effect of a sigma-1 receptor agonist, cutamesine dihydrochloride (SA4503), on photoreceptor cell death against light-induced damage[J]. Exp Eye Res, 2015,132:64-72. |
| [31] | Urfer R, Moebius H J, Skoloudik D, et al. Cutamesine stroke recovery study group. Phase Ⅱ trial of the sigma-1 receptor agonist cutamesine (SA4503) for recovery enhancement after acute ischemic stroke[J]. Stroke, 2014,45:3304-3310. |
/
| 〈 |
|
〉 |