Fas对镉激活PC12细胞线粒体凋亡通路的影响

doi:10.11843/j.issn.0366-6964.2021.08.026

Abstract

Abstract: In order to explore the role of Fas death receptor in rat pheochromocytoma cell line (PC12) apoptosis induced by cadmium (Cd) and its regulation mechanism on the mitochondrial pathway, Fas gene silencing PC12 cells were treated with 10 μmol·L^-1 Cd for 12 hours. The activation of BH3 interacting domain death agonist (BID), cysteine aspartate-specific protease-9 (caspase-9), cysteine aspartate-specific protease-3 (caspase-3), poly ADP ribose polymerase (PARP), the expression of Bcl-2 associated X protein (Bax), B-cell lymphoma/leukemia-2 (Bcl-2), apoptosis inducing factor (AIF), endonuclease G (Endo G), and the distribution of cytochrome C (Cyt C) in cells were detected by Western blot. Nuclear translocation of AIF was detected by immunofluorescence staining. The results showed that Cd significantly increased the tBID/BID and Bax/Bcl-2 ratios, the release of Cyt C from mitochondria into the cytosol, the activation of caspase-9, caspase-3, PARP, and the expression of AIF, Endo G (P<0.01). Meanwhile, Cd induced the nuclear translocation of AIF. Fas silencing significantly inhibited Cd-induced increase of the tBID/BID and Bax/Bcl-2 ratios, the release of Cyt C from mitochondria into the cytosol, the activation of caspase-3, PARP, the expression of AIF, Endo G (P<0.01). Cd-activated caspase-9 was significantly inhibited by Fas silencing (P<0.05). Cd-induced nuclear translocation of AIF was abated by Fas silencing. The above results indicate that PC12 cells apoptosis induced by Cd via the mitochondrial pathway is mediated by Fas.

Key words: cadmium, Fas, PC12 cells, apoptosis, mitochondrial pathway

CLC Number:

S856.9

WEN Shuangquan, CHEN Jie, WANG Li, ZOU Hui, GU Jianhong, LIU Xuezhong, BIAN Jianchun, LIU Zongping, YUAN Yan. Effects of Fas on Mitochondrial Apoptotic Pathway Activated by Cadmium in PC12 Cells[J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52(8): 2326-2333.

References 35

[1]	WANG B, DU Y L. Cadmium and its neurotoxic effects[J]. Oxid Med Cell Longev, 2013, 2013:898034.
[2]	YUAN Y, YANG J L, CHEN J, et al. Alpha-lipoic acid protects against cadmium-induced neuronal injury by inhibiting the endoplasmic reticulum stress eIF2α-ATF4 pathway in rat cortical neurons in vitro and in vivo[J]. Toxicology, 2019, 414:1-13.
[3]	ANDERSSON H, PETERSSON-GRAWÉ K, LINDQVIST E, et al. Low-level cadmium exposure of lactating rats causes alterations in brain serotonin levels in the offspring[J]. Neurotoxicol Teratol, 1997, 19(2):105-115.
[4]	MIN J Y, MIN K B. Blood cadmium levels and Alzheimer's disease mortality risk in older US adults[J]. Environ Health, 2016, 15(1):69.
[5]	HALDER S, KAR R, CHAKRABORTY S, et al. Cadmium level in brain correlates with memory impairment in F1 and F2 generation mice:improvement with quercetin[J]. Environ Sci Pollut Res Int, 2019, 26(10):9632-9639.
[6]	YUAN Y, BIAN J C, LIU X Z, et al. Oxidative stress and apoptotic changes of rat cerebral cortical neurons exposed to cadmium in vitro[J]. Biomed Environ Sci, 2012, 25(2):172-181.
[7]	TANG K K, LIU X Y, WANG Z Y, et al. Trehalose alleviates cadmium-induced brain damage by ameliorating oxidative stress, autophagy inhibition, and apoptosis[J]. Metallomics, 2019, 11(12):2043-2051.
[8]	LIU W, XU C, ZHAO H Y, et al. Osteoprotegerin induces apoptosis of osteoclasts and osteoclast precursor cells via the Fas/Fas ligand pathway[J]. PLoS One, 2015, 10(11):e0142519.
[9]	HE X Y, WU J, YUAN L Y, et al. Lead induces apoptosis in mouse TM3 Leydig cells through the Fas/FasL death receptor pathway[J]. Environ Toxicol Pharmacol, 2017, 56:99-105.
[10]	LIU G, YUAN Y, LONG M F, et al. Beclin-1-mediated autophagy protects against cadmium-activated apoptosis via the Fas/Fasl pathway in primary rat proximal tubular cell culture[J]. Sci Rep, 2017, 7(1):977.
[11]	NAGATA S. Fas ligand-induced apoptosis[J]. Annu Rev Genet, 1999, 33:29-55.
[12]	LUO X, BUDIHARDJO I, ZOU H, et al. Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors[J]. Cell, 1998, 94(4):481-490.
[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 protrct effect of NAC[D]. Yangzhou:Yangzhou University, 2016.(in Chinses)
[14]	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 Chinses)
[15]	LIU W, XU C, RAN D, et al. CaMKⅡ mediates cadmium induced apoptosis in rat primary osteoblasts through MAPK activation and endoplasmic reticulum stress[J]. Toxicology, 2018, 406-407:70-80.
[16]	WANG S S, REN X M, HU X D, et al. Cadmium-induced apoptosis through reactive oxygen species-mediated mitochondrial oxidative stress and the JNK signaling pathway in TM3 cells, a model of mouse Leydig cells[J]. Toxicol Appl Pharmacol, 2019, 368:37-48.
[17]	赵世文. α-硫辛酸对铅镉联合致大鼠大脑皮质毒性损伤的保护效应[D]. 扬州:扬州大学, 2018.ZHAO S W. The protective effects of α-lipoid-acid on toxic damage of cadmium and lead exposure in cerebral cortex of rats[D]. Yangzhou:Yangzhou University, 2018.(in Chinses)
[18]	ULLAH I, CHUNG K, OH J, et al. Intranasal delivery of a Fas-blocking peptide attenuates Fas-mediated apoptosis in brain ischemia[J]. Sci Rep, 2018, 8(1):15041.
[19]	ZHANG J F, SHI L L, ZHANG L, et al. MicroRNA-25 negatively regulates cerebral ischemia/reperfusion injury-induced cell apoptosis through Fas/FasL pathway[J]. J Mol Neurosci, 2016, 58(4):507-516.
[20]	YUAN Y, ZHANG Y J, ZHAO S W, et al. Cadmium-induced apoptosis in neuronal cells is mediated by Fas/FasL-mediated mitochondrial apoptotic signaling pathway[J]. Sci Rep, 2018, 8(1):8837.
[21]	SU L J, ZHANG J H, GOMEZ H, et al. Reactive oxygen species-induced lipid peroxidation in apoptosis, autophagy, and ferroptosis[J]. Oxid Med Cell Longev, 2019, 2019:5080843.
[22]	KUWANA T, MACKEY M R, PERKINS G, et al. Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane[J]. Cell, 2002, 111(3):331-342.
[23]	MARZO I, BRENNER C, ZAMZAMI N, et al. Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis[J]. Science, 1998, 281(5385):2027-2031.
[24]	YUAN Y, JIANG C Y, HU F F, et al. The role of mitogen-activated protein kinase in cadmium-induced primary rat cerebral cortical neurons apoptosis via a mitochondrial apoptotic pathway[J]. J Trace Elem Med Biol, 2015, 29:275-283.
[25]	SAELENS X, FESTJENS N, WALLE L V, et al. Toxic proteins released from mitochondria in cell death[J]. Oncogene, 2004, 23(16):2861-2874.
[26]	NAKABAYASHI J, SASAKI A. A mathematical model for apoptosome assembly:the optimal cytochrome c/Apaf-1 ratio[J]. J Theor Biol, 2006, 242(2):280-287.
[27]	CHAITANYA G V, ALEXANDER J S, BABU P P. PARP-1 cleavage fragments:signatures of cell-death proteases in neurodegeneration[J]. Cell Commun Signal, 2010, 8(1):31.
[28]	SAIRANEN T, SZEPESI R, KARJALAINEN-LINDSBERG M L, et al. Neuronal caspase-3 and PARP-1 correlate differentially with apoptosis and necrosis in ischemic human stroke[J]. Acta Neuropathol, 2009, 118(4):541-552.
[29]	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 protection of NAC in rat's neuronal cells[D]. Yangzhou:Yangzhou University, 2014.(in Chinses)
[30]	YU W R, LIU T Y, FEHLINGS T K, et al. Involvement of mitochondrial signaling pathways in the mechanism of Fas-mediated apoptosis after spinal cord injury[J]. Eur J Neurosci, 2009, 29(1):114-131.
[31]	SUSIN S A, LORENZO H K, ZAMZAMI N, et al. Molecular characterization of mitochondrial apoptosis-inducing factor[J]. Nature, 1999, 397(6718):441-446.
[32]	VAN LOO G, SCHOTTE P, VAN GURP M, et al. Endonuclease G:a mitochondrial protein released in apoptosis and involved in caspase-independent DNA degradation[J]. Cell Death Differ, 2001, 8(12):1136-1142.
[33]	BAJT M L, COVER C, LEMASTERS J J, et al. Nuclear translocation of endonuclease G and apoptosis-inducing factor during acetaminophen-induced liver cell injury[J]. Toxicol Sci, 2006, 94(1):217-225.
[34]	LEE S Y, OH J Y, LEE M J, et al. Anti-apoptotic mechanism and reduced expression of phospholipase D in spontaneous and Fas-stimulated apoptosis of human neutrophils[J]. Eur J Immunol, 2004, 34(10):2760-2770.
[35]	SUSIN S A, ZAMZAMI N, CASTEDO M, et al. The central executioner of apoptosis:multiple connections between protease activation and mitochondria in Fas/APO-1/CD95-and ceramide-induced apoptosis[J]. J Exp Med, 1997, 186(1):25-37.

Effects of Fas on Mitochondrial Apoptotic Pathway Activated by Cadmium in PC12 Cells

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