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WANG Yan, PING Fengfeng, ZHOU Danli, CHEN Yanhua, LING Jingjing. Masitinib alleviated cerebral ischemia/reperfusion injury by inhibiting autophagy and apoptosis[J]. Journal of China Pharmaceutical University, 2021, 52(2): 227-235. DOI: 10.11665/j.issn.1000-5048.20210212
Citation: WANG Yan, PING Fengfeng, ZHOU Danli, CHEN Yanhua, LING Jingjing. Masitinib alleviated cerebral ischemia/reperfusion injury by inhibiting autophagy and apoptosis[J]. Journal of China Pharmaceutical University, 2021, 52(2): 227-235. DOI: 10.11665/j.issn.1000-5048.20210212

Masitinib alleviated cerebral ischemia/reperfusion injury by inhibiting autophagy and apoptosis

Funds: This study was supported by the Scientific Research Project of Wuxi Health Commission (No.Q202010); the Six Talent Peak Project of Jiangsu Province (No.YY-128) and Wuxi Taihu Talent Plan Top Talents Project (No.BJ2020088, No.BJ2020001)
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  • Received Date: September 25, 2020
  • Revised Date: March 24, 2021
  • To investigate the neuroprotective effect and possible mechanism of masitinib on cerebral ischemia-reperfusion injury in rats, healthy adult male Sprague-Dawley rats were divided into sham group (n = 12), model group (n = 12), masitinib low dosage group (n = 12), masitinib middle dosage group (n = 12), and masitinib high dosage group (n = 12). All rats was subjected to middle cerebral artery occlusion (MCAO) for two hours and reperfusion except sham group, and received treatment twice per day for 7 days once reperfusion started.Neurological score, infarct volume, and brain water content were detected; some autophagic markers, apoptotic and inflammatory cytokines were evaluated by Western blot and PCR after 7 d of reperfusion. Treatment with masitinib significantly ameliorated neurologic deficit, infarct volume and brain water after I/R injury. Masitinib also decreased the ratio of LC3II/I and the expression of Beclin-1 and increased the expression of p62 in the brain tissues of rats with I/R injury.Furthermore, it could inhibit apoptosis-related proteins and NF-κB expression. Masitinib could relieve the cerebral ischemia-reperfusion injury in rats through inhibiting autophagy and apoptosis.
  • [1]
    . Lancet, 2008, 371(9624): 1612-1623.
    [2]
    Li XM, Fan WX. Effects of pnu-282987 on neuronal apoptosis and learning and memory ability after cerebral ischemia-reperfusion injury in rats[J]. J China Pharm Univ (中国药科大学学报), 2020, 51(2): 193-197.
    [3]
    Stankov K, Popovic S, Mikov M. C-KIT signaling in cancer treatment[J]. Curr Pharm Des, 2014, 20(17): 2849-2880.
    [4]
    Feng ZC, Riopel M, Popell A, et al. A survival Kit for pancreatic beta cells: stem cell factor and c-Kit receptor tyrosine kinase[J]. Diabetologia, 2015, 58(4): 654-665.
    [5]
    Kawada H, Takizawa S, Takanashi T, et al. Administration of hematopoietic cytokines in the subacute phase after cerebral infarction is effective for functional recovery facilitating proliferation of intrinsic neural stem/progenitor cells and transition of bone marrow-derived neuronal cells[J]. Circulation, 2006, 113(5): 701-710.
    [6]
    Toth ZE, Leker RR, Shahar T, et al. The combination of granulocyte colony-stimulating factor and stem cell factor significantly increases the number of bone marrow-derived endothelial cells in brains of mice following cerebral ischemia[J]. Blood, 2008, 111(12): 5544-5552.
    [7]
    Longa EZ, Weinstein PR, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats[J]. Stroke, 1989, 20(1): 84-91.
    [8]
    Pan J, Konstas AA, Bateman B, et al., Reperfusion injury following cerebral ischemia: pathophysiology, MR imaging, and potential therapies[J]. Neuroradiology, 2007. 49(2): 93-102.
    [9]
    Fernandez-Lopez D, Faustino J, Daneman R, et al., Blood-brain barrier permeability is increased after acute adult stroke but not neonatal stroke in the rat[J]. J Neurosci, 2012, 32(28): 9588-9600.
    [10]
    Hahn KA, Ogilvie G, Rusk T, et al., Masitinib is safe and effective for the treatment of canine mast cell tumors[J]. J Vet Intern Med, 2008, 22(6): 1301-1309.
    [11]
    Humbert M, Castéran N, Letard S, et al., Masitinib combined with stan-dard gemcitabine chemotherapy: in vitro and in vivo studies in humanpancreatic tumour cell lines and ectopic mouse model[J]. PLoS One, 2010, 5(3): e9430.
    [12]
    Sun Y, Zhu Y, Zhong X, et al. Crosstalk between autophagy and cerebral Ischemia[J]. Front Neurosci, 2019, 12: 1022.
    [13]
    Kim KA, Shin D, Kim JH, et al. Role of autophagy in endothelial damage and blood-brain barrier disruption in ischemic stroke[J]. Stroke, 2018, 49(6): 1571-1579.
    [14]
    Kriel J, Loos B. The good, the bad and the autophagosome: exploring unanswered questions of autophagy-dependent cell death[J]. Cell Death Differ, 2019, 26(4): 640-652.
    [15]
    Wei YM, Ren JH, Luan ZH, et al. Effects of various autophagy regulators on the expression of autophagy markers LC3 Ⅱ and p62[J]. J China Pharm Univ (中国药科大学学报), 2018, 49(3): 341-347.
    [16]
    Klionsky DJ, Cuervo AM, Seglen PO. Methods for monitoring autophagy from yeast to human[J]. Autophagy, 2007, 3(3): 181-206.
    [17]
    Bjorkoy G, Lamark T, Brech A, et al. p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death[J]. J Cell Biol, 2005, 171(4): 603-614.
    [18]
    Liang XH, Jackson S, Seaman M, et al. Induction of autophagy and inhibition of tumorigenesis by Beclin 1[J]. Nature, 1999, 402(6762): 672-676.
    [19]
    Au AK, Aneja RK, Bay?r H, et al. Autophagy biomarkers Beclin 1 and p62 are increased in cerebrospinal fluid after traumatic brain injury[J]. Neurocrit Care, 2017, 26(3): 348-355.
    [20]
    Dai SH, Chen T, Li X, et al. Sirt3 confers protection against neuronal ischemia by inducing autophagy: involvement of the AMPK-mTOR pathway[J]. Free Radic Biol Med, 2017, 108: 345-353.
    [21]
    Trocoli A, Djavaheri-Mergn M. The complex interplay between autophagy and NF-κB signaling pathways in cancer cells[J]. Am J Cancer Res, 2011, 1(5): 629-649.
    [22]
    Purcell NH, Tang G, Tu C, et al., Activation of NF-κB is required for hypertrophic growth of primary rat neonatal ventricular cardiomyocytes[J]. Proc Natl Acad Sci U S A, 2001, 98(12): 6668-6673.
    [23]
    Liang XH, Jackson S, Seaman M, et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1[J]. Nature, 1999, 402(6762): 672-676.
    [24]
    Qi ZF, Dong W, Shi WJ, et al. Bcl-2 phosphorylation triggers autophagy switch and reduces mitochondrial damage in limb remote ischemic conditioned rats after ischemic stroke[J]. Transl Stroke Res, 2015, 6(3): 198-206.
    [25]
    Boya P, González-Polo RA, Gasares N, et al. Inhibition of macroautophagy triggers apoptosis[J]. Mol Cell Biol, 2005, 25(3): 1025-1040.
    [26]
    Pattingre S, Tassa A, Qu XP, et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy[J]. Cell, 2005, 122(6): 927-939.
    [27]
    Takacs-Vellai K, Vellai T, Puoti A, et al. Inactivation of the autophagy gene bec-1 triggers apoptotic cell death in C. elegans[J]. Curr Biol, 2005, 15(16): 1513-1517.
    [28]
    Zhang XN, Yan HJ, Yuan Y, et al. Cerebral ischemia-reperfusion-induced autophagy protects against neuronal injury by mitochondrial clearance[J]. Autophagy, 2013, 9(9): 1321-1333.
    [29]
    Jin ZY, Li Y, Pitti R, et al. Cullin3-based polyubiquitination and p62-dependent aggregation of caspase-8 mediate extrinsic apoptosis signaling[J]. Cell, 2009, 137(4): 721-735.
    [30]
    Hou W, Han J, Lu CS, et al. Autophagic degradation of active caspase-8: a crosstalk mechanism between autophagy and apoptosis[J]. Autophagy, 2010, 6(7): 891-900.
    [31]
    Pan JA, Fan YJ, Gandhirajan RK, et al. Hyperactivation of the mammalian degenerin MDEG promotes caspase-8 activation and apoptosis[J]. J Biol Chem, 2013, 288(5): 2952-2963.
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