Fas/FasL通路对镉激活PC12细胞MAPK通路的影响

doi:10.11843/j.issn.0366-6964.2021.07.025

Abstract

Abstract: To study the effect of Fas/FasL pathway on cadmium-activated MAPK pathway in PC12 cells, PC12 cells with non-specific sequences inserted and Fas gene silenced were treated with 10 μmol·L^-1 CdAc₂ respectively for 12 h, PC12 cells were treated with 10 μmol·L^-1CdAc₂ and 40 μmol·L^-1 Z-IETD-FMK (caspase-8 specific inhibitor) alone or in combination for 12 h. The expression of Fas/FasL pathway-related proteins Fas, FasL, Fas-associated death domain protein (FADD), Cleaved caspase-8, Death domain associated protein (Daxx), Apptosis signal-regulating kinase 1 (ASK1) and MAPK pathway-related proteins ERK1/2, JNK1/2, p-ERK1/2, p-JNK1/2 were detected by Western blot. The morphological changes of apoptosis were detected by Hoechst33258 fluorescence staining, and the apoptosis rate was detected by flow cytometry. The results showed that Fas shRNA lentivirus significantly inhibited the increase of Fas/FasL pathway related-proteins expression and apoptosis rate in PC12 cells induced by cadmium (P<0.01), and alleviated the morphological changes of cell apoptosis caused by cadmium in PC12 cells. In addition, Fas shRNA and Z-IETD-FMK could significantly inhibit the increase of cadmium-induced phosphorylation levels of MAPK pathway-related proteins ERK1/2 and JNK1/2 in PC12 cells (P<0.01). Our results indicate that the regulation of Fas/FasL pathway on the MAPK pathway is involved in cadmium-induced apoptosis in PC12 cells.

Key words: cadmium, PC12 cell, apoptosis, Fas/FasL pathway, MAPK pathway

CLC Number:

S856.9

WANG Li, CHEN Jie, WEN Shuangquan, ZOU Hui, GU Jianhong, LIU Xuezhong, BIAN Jianchun, LIU Zongping, YUAN Yan. Effect of Fas/FasL Pathway on MAPK Pathway Activated by Cadmium in PC12 Cells[J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52(7): 2034-2043.

References 30

[1]	HUAT T J, CAMATS-PERNA J, NEWCOMBE E A, et al. Metal toxicity links to alzheimer's disease and neuroinflammation[J]. J Mol Biol, 2019, 431(9):1843-1868.
[2]	KARRI V, SCHUHMACHER M, KUMAR V. Heavy metals (Pb, Cd, As and MeHg) as risk factors for cognitive dysfunction:A general review of metal mixture mechanism in brain[J]. Environ Toxicol Pharmacol, 2016, 48:203-213.
[3]	RANI A, KUMAR A, LAL A, et al. Cellular mechanisms of cadmium-induced toxicity:a review[J]. Int J Environ Health Res, 2014, 24(4):378-399.
[4]	HUANG C C, KUO C Y, YANG C Y, et al. Cadmium exposure induces pancreatic β-cell death via a Ca2+-triggered JNK/CHOP-related apoptotic signaling pathway[J]. Toxicology, 2019, 425:152252.
[5]	EL HENI J, MESSAOUDI I, BEN CHAOUACHA-CHEKIR R. Effects of sub-chronic exposure to cadmium on some parameters of calcium and iodine metabolisms in the Shaw's jird Meriones shawi[J]. Environ Toxicol Pharmacol, 2012, 34(2):136-143.
[6]	袁燕, 张雅静, 陈洁, 等. Fas/FasL信号通路在镉致PC12细胞凋亡中的作用及NAC的保护效应[J]. 中国兽医科学, 2018, 48(10):1318-1324.YUAN Y, ZHANG Y J, CHEN J, et al. Role of Fas/FasL signaling pathway in apoptosis of PC12 cells induced by cadmium and protective effect of NAC[J]. Chinese Veterinary Science, 2018, 48(10):1318-1324. (in Chinese)
[7]	WANG M, SU P. The role of the Fas/FasL signaling pathway in environmental toxicant-induced testicular cell apoptosis:an update[J]. Syst Biol Reprod Med, 2018, 64(2):93-102.
[8]	MORRISON D K. MAP kinase pathways[J]. Cold Spring Harb Perspect Biol, 2012, 4(11):a011254.
[9]	徐卉. 镉致大鼠大脑皮质神经元凋亡的线粒体途径[D]. 扬州:扬州大学, 2013.XU H. Mitochondrial pathway of cadmium-induced apoptosis in primary rat cerebral cortical neurons culture[D]. Yangzhou:Yangzhou University, 2013. (in Chinese)
[10]	江辰阳, 徐卉, 胡飞飞, 等. MAPKs信号通路在镉致大鼠大脑皮质神经细胞毒性中的作用[J]. 中国兽医学报, 2014, 34(4):628-632.JIANG C Y, XU H, HU F F, et al. The effect of cadmium on MAPKs activities of rat primary cerebral cortical neuron cultured in vitro[J]. Chinese Journal of Veterinary Science, 2014, 34(4):628-632. (in Chinese)
[11]	LIU W H, CHENG Y C, CHANG L S. ROS-mediated p38αMAPK activation and ERK inactivation responsible for upregulation of Fas and FasL and autocrine Fas-mediated cell death in Taiwan cobra phospholipase A2-treated U937 cells[J]. J Cell Physiol, 2009, 219(3):642-651.
[12]	GALLAGHER S F, PENG Y H, HAINES K, et al. Fas/FasL play a central role in pancreatitis-induced hepatocyte apoptosis[J]. J Gastrointest Surg, 2005, 9(4):467-475.
[13]	张雅静. Fas/FasL信号转导通路在镉致神经细胞凋亡中的作用及NAC的保护效应[D]. 扬州:扬州大学, 2016.ZHANG Y J. Role of Fas/FasL signaling pathway in cadmium induced neural apoptosis and protect effect of NAC[D]. Yangzhou:Yangzhou University, 2016. (in Chinese)
[14]	D'ARCY M S. Cell death:a review of the major forms of apoptosis, necrosis and autophagy[J]. Cell Biol Int, 2019, 43(6):582-592.
[15]	孙建华, 李雁. Fas/FasL系统在肿瘤细胞凋亡中的研究进展[J]. 医学综述, 2015, 21(20):3694-3696.SUN J H, LI Y. The research progress of Fas/FasL system in tumor cell apoptosis[J]. Medical Recapitulate, 2015, 21(20):3694-3696. (in Chinese)
[16]	CHEN L, XU B S, LIU L, et al. Cadmium induction of reactive oxygen species activates the mTOR pathway, leading to neuronal cell death[J]. Free Radic Biol Med, 2011, 50(5):624-632.
[17]	JIANG J H, GE G, GAO K, et al. Calcium signaling involvement in cadmium-induced astrocyte cytotoxicity and cell death through activation of MAPK and PI3K/Akt signaling pathways[J]. Neurochem Res, 2015, 40(9):1929-1944.
[18]	YANG Z Q, YANG S F, QIAN S Y, et al. Cadmium-induced toxicity in rat primary mid-brain neuroglia cultures:role of oxidative stress from microglia[J]. Toxicol Sci, 2007, 98(2):488-494.
[19]	BEN P L, ZHANG Z P, XUAN C X, et al. Protective Effect of L-theanine on cadmium-induced apoptosis in PC12 cells by inhibiting the mitochondria-mediated pathway[J]. Neurochem Res, 2015, 40(8):1661-1670.
[20]	江辰阳. 镉致大鼠神经细胞凋亡的线粒体途径及NAC的保护作用[D]. 扬州:扬州大学, 2014.JIANG C Y. Cadmium induces apoptosis through the mitochondrial pathway and the protective of NAC in rat's neuronal cells[D]. Yangzhou:Yangzhou University, 2014. (in Chinese)
[21]	WANG J, LI W, MIN J, et al. Fas siRNA reduces apoptotic cell death of allogeneic-transplanted hepatocytes in mouse spleen[J]. Transplant Proc, 2003, 35(4):1594-1595.
[22]	LI J H, QIAN L Y, DOWLING J P, et al. Daxx plays a novel role in T cell survival but is dispensable in Fas-induced apoptosis[J]. PLoS One, 2017, 12(3):e0174011.
[23]	LIU F, DU Z Y, HE J L, et al. FTH1 binds to Daxx and inhibits Daxx-mediated cell apoptosis[J]. Mol Biol Rep, 2012, 39(2):873-879.
[24]	WANG L W, YANG J K, KABALEESWARAN V, et al. The Fas-FADD death domain complex structure reveals the basis of DISC assembly and disease mutations[J]. Nat Struct Mol Biol, 2010, 17(11):1324-1329.
[25]	BAYRAM S, KIZILAY G, TOPCU-TARLADA-CALISIR Y. Evaluation of the Fas/FasL signaling pathway in diabetic rat testis[J]. Biotech Histochem, 2016, 91(3):204-211.
[26]	SALVESEN G S, RIEDL S J. Structure of the Fas/FADD complex:a conditional death domain complex mediating signaling by receptor clustering[J]. Cell Cycle, 2009, 8(17):2723-2727.
[27]	KIM S M, PARK J G, BAEK W K, et al. Cadmium specifically induces MKP-1 expression via the glutathione depletion-mediated p38 MAPK activation in C6 glioma cells[J]. Neurosci Lett, 2008, 440(3):289-293.
[28]	JIANG C Y, YUAN Y, HU F F, et al. Cadmium induces PC12 cells apoptosis via an extracellular signal-regulated kinase and c-Jun N-terminal kinase-mediated mitochondrial apoptotic pathway[J]. Biol Trace Elem Res, 2014, 158(2):249-258.
[29]	LVSCHEN S, FALK M, SCHERER G, et al. The Fas-associated death domain protein/caspase-8/c-FLIP signaling pathway is involved in TNF-induced activation of ERK[J]. Exp Cell Res, 2005, 310(1):33-42.
[30]	KHELIFI A F, D'ALCONTRES M S, SALOMONI P. Daxx is required for stress-induced cell death and JNK activation[J]. Cell Death Differ, 2005, 12(7):724-733.

Effect of Fas/FasL Pathway on MAPK Pathway Activated by Cadmium in PC12 Cells

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