Research advance on molecular mechanism of apoptosis induced by heavy metal-associated calcium overload
XIAO Yuan-yuan1, YIN Xiao-chen2, ZENG Ming1
1.Department of Health Toxicology, Xiangya School of Public Health, Central South University, Changsha, Hunan 410078, China; 2. Hunan Provincial Center for Disease Control and Prevention, Changsha, Hunan 410005, China
Abstract:The pollution of heavy metals in the environment is becoming more and more serious, and the main reason is the arbitrary discharge of industrial three wastes. Heavy metals such as cadmium (Cd), chromium (Cr), mercury (Hg), lead (Pb) and arsenic (As) in the environment can enter cells in ionic form through a variety of ways, and result in continuously increase of Ca2+ concentration in cytoplasm and Ca2+ overload. Finally, they induce apoptosis and cause serious toxicity to important organs in vivo. The mechanisms may be related to the destruction of cell membrane structure and function, mitochondrial damage and endoplasmic reticulum stress, activation of Ca2+-dependent enzymes, overexpression of reactive oxygen species, changes of Bcl-2 and Caspases family proteins. In this paper, we review the molecular mechanism of cell apoptosisinduced by heavy metal-associated calcium overloadand provide references for studying heavy metal-related toxicity and its mechanism.
[1] Tchounwou PB, Yedjou CG, Patlolla AK, et al. Heavy metal toxicity and the environment[J]. Exp Suppl,2012, 101:133-164. [2] 刘欣梅,项黎新,邵健忠,等. 重金属诱导细胞凋亡的分子机制[J]. 细胞生物学杂志, 2004,26(3):235-240. [3] Siddarth M, Chawla D, Raizada A, et al. Lead-induced DNA damage and cell apoptosis in human renal proximal tubular epithelial cell: attenuation via N-acetyl cysteine and tannic acid[J]. J Biochem Mol Toxicol, 2018, 32(3):e22038. [4] Ramos-Trevino J, Bassol-Mayagoitia S, Hernandez-Ibarra JA, et al. Toxic effect of cadmium, lead, and arsenic on the sertoli cell: mechanisms of damage involved[J]. DNA Cell Biol, 2018, 37(7):600-608. [5] Fox DA, He L, Poblenz AT, et al. Lead-induced alterations in retinal cGMP phosphodiesterase trigger calcium overload, mitochondrial dysfunction and rod photoreceptor apoptosis[J]. Toxicol Lett,1998, 102-103:359-361. [6] Kim SH, Sharma RP. Cytotoxicity of inorganic mercury in murine T and B lymphoma cell lines:involvement of reactive oxygen species, Ca2+ homeostasis, and cytokine gene expression[J]. Toxicol In Vitro, 2003, 17(4):385-395. [7] Peacock M. Calcium metabolism in health and disease[J]. Clin J Am Soc Nephrol, 2010, 5 Suppl 1:S23-S30. [8] Yang Z, Hayes JJ. The divalent cations Ca2+ and Mg2+ play specific roles in stabilizing histone-DNA interactions within nucleosomes that are partially redundant with the core histone tail domains[J]. Biochemistry, 2011, 50(46):9973-9981. [9] Sigel A, Operschall BP, Sigel H. Complex formation of lead (II) with nucleotides and their constituents[J]. Met Ions Life Sci, 2017, 17. [10] 马燕,张硕,滕月. 钙通道与钙通道病相关研究进展[J]. 基层医学论坛, 2007,5:263-265. [11] Guerini D, Coletto L, Carafoli E. Exporting calcium from cells[J]. Cell Calcium, 2005, 38(3/4):281-289. [12] Ahlijanian MK, Cooper DM. Antagonism of calmodulin-stimulated adenylate cyclase by trifluoperazine, calmidazolium and W-7 in rat cerebellar membranes[J]. J Pharmacol Exp Ther,1987, 241(2):407-414. [13]Santulli G, Nakashima R, Yuan Q, et al. Intracellular calcium release channels:an update[J]. J Physiol, 2017, 595(10):3041-3051. [14] Berchtold MW, Villalobo A. The many faces of calmodulin in cell proliferation, programmed cell death, autophagy, and cancer[J]. Biochim Biophys Acta, 2014, 1843 (2):398-435. [15] Barritt GJ, Litjens TL, Castro J, et al. Store-operated Ca2+ channels and microdomains of Ca2+ in liver cells[J]. Clin Exp Pharmacol Physiol, 2009, 36(1):77-83. [16] Afroze T, Yang G, Khoshbin A, et al. Calcium efflux activity of plasma membrane Ca2+ATPase-4 (PMCA4) mediates cell cycle progression in vascular smooth muscle cells[J]. J Biol Chem, 2014, 289(10):7221-7231. [17] Zhou X, Hao W, Shi H, et al. Calcium homeostasis disruption - a bridge connecting cadmium-induced apoptosis, autophagy and tumorigenesis[J]. Oncol Res Treat, 2015, 38(6):311-315. [18] 王随心,张玉华,李向阳,等. 重金属生精细胞毒性研究进展[J]. 环境与健康杂志, 2011,28(4):367-372. [19] Xie Z, Zhang Y, Li A, et al. Cd-induced apoptosis was mediated by the release of Ca2+ from intracellular Ca storage[J]. Toxicol Lett, 2010, 192(2):115-118. [20] 林秀武,李艳华,牟颖,等. 甲基汞对细胞膜损伤作用[J]. 中华预防医学杂志, 1995,29(1):9-12. [21] 肖银霞,李金龙,徐世文,等. 镉、硒、氟、铜、锌、磷对细胞膜影响的研究进展[J]. 中国地方病学杂志, 2006, 25(2):225-226. [22] Pathak N, Mitra S, Khandelwal S. Cadmium induces thymocyte apoptosis via caspase-dependent and caspase-independent pathways[J]. J Biochem Mol Toxicol, 2013, 27(3):193-203. [23] Bernardi P. The mitochondrial permeability transition pore:a mystery solved[J]. Front Physiol, 2013, 4:95. [24] 肖经纬,钟才高,李斌. 六价铬诱导L-02肝细胞凋亡与线粒体功能损伤的关系研究[J]. 卫生研究, 2006, 35(4):416-418. [25] 刘巍, 魏兴龙, 杨天瑶, 等. 线粒体钙超载激活线粒体凋亡途径在甲基汞致神经元凋亡中的作用[J]. 实用预防医学, 2018, 25(12):1409-1412. [26] 李静慧,徐兆发. 镉致肾细胞凋亡机制的研究进展及防治[J]. 毒理学杂志, 2014,28(4):319-322. [27] Lee CH, Yu HS. Role of mitochondria, ROS, and DNA damage in arsenic induced carcinogenesis[J]. Front Biosci (Schol Ed), 2016, 8:312-320. [28] 徐斌, 徐兆发, 邓宇, 等. 地卓西平对甲基汞致大鼠脑皮质细胞内钙稳态失调的影响[J]. 实用预防医学, 2011, 18(4):601-603. [29] Bahar E, Kim H, Yoon H. ER stress-mediated signaling: action potential and Ca2+as key Players[J]. Int J Mol Sci, 2016, 17(9):E1558. [30] Liu F, Inageda K, Nishitai G, et al. Cadmium induces the expression of Grp78, an endoplasmic reticulum molecular chaperone, in LLC-PK1 renal epithelial cells[J]. Environ Health Perspect, 2006, 114(6):859-864. [31] Hechtenberg S, Beyersmann D. Inhibition of sarcoplasmic reticulum Ca2+-ATPase activity by cadmium, lead and mercury[J]. Enzyme, 1991, 45(3):109-115. [32] Liang Q, Zhang Y, Zeng M, et al. The role of IP3R-SOCCs in Cr(vi)-induced cytosolic Ca2+overload and apoptosis in L-02 hepatocytes[J]. Toxicol Res (Camb), 2018, 7(3):521-528. [33] Fox DA, Srivastava D, Poblenz A, et al. Lead-induced alterations in gene expression and activity of retinal cGMP PDE results in calcium overload and rod-selective apoptosis[J]. Toxicology in Vitro, 1998, 12(5):597-598. [34] Butler RA, Roesijadi G. Disruption of metallothionein expression with antisense oligonucleotides abolishes protection against cadmium cytotoxicity in molluscan hemocytes[J]. Toxicol Sci, 2001, 59(1):101-107. [35] 赵兰,李文军,王金涛,等. 钙稳态失衡在氯化镧诱导MDCC-MSB1细胞凋亡中的作用[J]. 中国家禽, 2008, 30(3):9-12. [36] 王莉,常彦忠,段相林. 铁离子对Caco-2细胞内钙离子转运的影响及钙离子浓度变化与细胞凋亡关系的研究[J]. 解剖学报, 2005,36 (2):177-181. [37] Schanne FA, Long GJ, Rosen JF. Lead induced rise in intracellular free calcium is mediated through activation of protein kinase C in osteoblastic bone cells[J]. Biochim Biophys Acta, 1997, 1360(3):247-254. [38] Jiang H, Zhang C, Tang Y, et al. The regulator of calcineurin 1 increases adenine nucleotide translocator 1 and leads to mitochondrial dysfunctions [J]. J Neurochem,2017, 140(2):307-319. [39] 向本琼,周捷,魏群. 钙调神经磷酸酶在CaM,Mn2+存在时的构象变化[J]. 科学通报, 1995 ,40(5):460-463. [40] Cheng J, Tang W, Su Z, et al. Calcineurin subunit B promotes TNF-alpha-induced apoptosis by binding to mitochondria and causing mitochondrial Ca2+ overload[J]. Cancer Lett, 2012, 321(2):169-178. [41] Shibasaki F, Hallin U, Uchino H. Calcineurin as a multifunctional regulator[J]. J Biochem, 2002, 131(1):1-15. [42] 杨云芬,李文芳,李济超. 铅的中枢神经毒性机制研究进展[J]. 中国工业医学杂志, 2012, 25(4):274-276. [43] Sinha K, Das J, Pal PB, et al. Oxidative stress:the mitochondria-dependent and mitochondria-independent pathways of apoptosis critical role of calcium overloading in cadmium-induced apoptosis in mouse thymocytes[J]. Arch Toxicol,2013, 87(7):1157-1180. [44] Jazvinscak JM, Vlainic J, Radovanovic V, et al. Effects of copper overload in P19 neurons:impairment of glutathione redox homeostasis and crosstalk between caspase and calpain protease systems in ROS-induced apoptosis[J]. Biometals, 2014,27(6):1303-1322. [45] 谢颖. 线粒体损伤拮抗剂在Cr(Ⅵ)所致肝细胞凋亡中的保护作用[D].长沙: 中南大学,2014. [46] Gasparottolino EP, Tognon R,Ferreira AF, et al. Deregulated expression of A1, Bcl-2, Bcl-xL, and Mcl-1 antiapoptotic proteins and Bid, Bad, and Bax proapoptotic genes in polycythemia vera patients[J]. Braz J Pharm Sci, 2011, 47(4):873-886. [47] Scorrano L, Oakes SA, Opferman JT, et al. BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis[J]. Science, 2003, 300(5616):135-139. [48] Danial NN, Gramm CF, Scorrano L, et al. BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis [J]. Nature, 2003, 424(6951):952-956. [49] Nutt LK, Chandra J, Pataer A, et al. Bax-mediated Ca2+ mobilization promotes cytochrome c release during apoptosis [J]. J Biol Chem,2002, 277(23):20301-20308. [50] Lu Y, Chen W, Lin C, et al. The protective effects of propofol against CoCl2-induced HT22 cell hypoxia injury via PP2A/CAMKIIalpha/nNOS pathway[J]. BMC Anesthesiol, 2017, 17(1):32. [51] He L, Perkins GA, Poblenz AT, et al. Bcl-xL overexpression blocks bax-mediated mitochondrial contact site formation and apoptosis in rod photoreceptors of lead-exposed mice[J]. Proc Natl Acad Sci U S A, 2003, 100(3):1022-1027. [52] 杨涛,费振海,钟兴明. Caspase家族与细胞凋亡的研究进展[J]. 浙江医学,2018, 40(18):2083-2087. [53] 薛全福,王振纲. 钙离子和细胞凋亡及药物调控[J]. 中国全科医学,2009, 12(12):1126-1128. [54] Wang SH, Shih YL, Ko WC, et al. Cadmium-induced autophagy and apoptosis are mediated by a calcium signaling pathway[J]. Cell Mol Life Sci, 2008, 65(22):3640-3652. [55] Wang SH, Shih YL, Lee CC, et al. The role of endoplasmic reticulum in cadmium-induced mesangial cell apoptosis[J]. Chem Biol Interact,2009,181(1):45-51. [56] 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. [57]Shen HM, Dong SY, Ong CN. Critical role of calcium overloading in cadmium-induced apoptosis in mouse thymocytes[J]. Toxicol Appl Pharmacol, 2001, 171(1):12-19. [58] Wang MG, Li WH, Wang XY, et al. CaMKII is involved in subcellular Ca2+redistribution-induced endoplasmic reticulum stress leading to apoptosis in primary cultures of rat proximal tubular cells exposed to lead [J]. Oncotarget,2017, 8(53):91162-91173.