DOI: 10.14704/nq.2018.16.5.1360

Influence of Cadmium on Nerve Cells of the Brain and the Neuroprotective Effect of Ca2+ Chelator and N-Acetyl-L-Cysteine

Zhongming Han, Xu Guo, Yu Si, Yunhe Wang, Xin Tian


This paper discussed the mechanism of damage and apoptosis caused by cadmium (Cd) to the nerve cells of the brain and the influence of Cd on the mRNA expression of Bcl-2 and NO synthase (NOS) genes. In addition, the protective influence of BAPTA-AM and N-Acetyl-L-cysteine (NAC) to the nerve cells was analyzed. Experiments were conducted to measure cell survival and concentrations of Ca2+ and ROS under different concentration of cadmium acetate. The results showed that with the increase in the concentration of cadmium acetate, the survival of nerve cells declined dramatically, while the intercellular Ca2+ and ROS concentrations increased significantly. This indicated considerable damage caused by Cd to the nerve cells. The mRNA expression of Bcl-2 decreased significantly with the increase in Cd concentration, while the mRNA expression of Bax increased to varying degrees. At a higher concentration of Bcl-2, Bcl-2/Bax heterodimer was detected in nerve cells, which slowed down the apoptosis of the cells; at a low concentration of Bcl-2, Bcl-2/Bax homodimer was formed, thus accelerating the apoptosis of the nerve cells. Fluorescence staining showed that the nerve cells in the control group were intact, uniformly stained and had elliptical nuclei. For the experimental group, the nuclei in most cells shrank in size or even became fragmented due to the presence of Cd. BAPTA-AM reversed the sudden increase of Ca2+ concentration in the nerve cells treated by Cd, while NAC reduced cell apoptosis by inhibiting the breaking and mutation of the DNA strand in cells. Compared with BAPTA-AM, NAC exhibited less significant inhibitory effect on Cd-induced cell apoptosis and offered limited neuroprotective effect on nerve cells.


Nerve Cell of the Brain, Cadmium, Cell Apoptosis, mRNA Expression, NAC, Calcium Chelator

Full Text:



Antonio MT, Corpas I, Leret ML. Neurochemical changes in newborn rat's brain after gestational cadmium and lead exposure. Toxicology Letters 1999; 104(1–2): 1-9.

Cantarella G, Lempereur L, D'Alcamo MA, Risuglia N, Cardile V, Pennisi, G. Trail interacts redundantly with nitric oxide in rat astrocytes: potential contribution to neurodegenerative processes. Journal of Neuroimmunology 2007; 182(1): 41-47.

Chargui A, Zekri S, Jacquillet G, Rubera I, Ilie M, Belaid A, Duranton C, Tauc M, Hofman P, Poujeol P, El May MV. Cadmium-induced autophagy in rat kidney: an early biomarker of subtoxic exposure. Toxicological Sciences 2011; 121(1):31-42.

Dong Z, Wang L, Xu J, Li Y, Zhang Y, Zhang S. Promotion of autophagy and inhibition of apoptosis by low concentrations of cadmium in vascular endothelial cells. Toxicology in Vitro 2009; 23(1): 105-10.

Green DR. Apoptotic pathways: ten minutes to dead. Cell 2005; 121(5): 671-74.

Guix FX, Uribesalgo I, Coma M, Muñoz FJ. The physiology and pathophysiology of nitric oxide in the brain. Progress in Neurobiology 2005; 76(2): 126-52.

Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri ES, Baehrecke EH. Classification of cell death: recommendations of the nomenclature committee on cell death. Cell Death & Differentiation 2009; 12 Suppl 2(1): 1463-67.

Lin W, Jin C, Chen DW, Liu XZ, Hao L, Liu ZP. Role of oxidative stress, apoptosis, and intracellular homeostasis in primary cultures of rat proximal tubular cells exposed to cadmium. Biological Trace Element Research 2009; 127(1): 53-60

Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative pcr and the 2(-delta delta c(t)) method. Methods 2012; 25(4): 402-08.

Maiuri MC, Zalckvar E, Kimchi A, Kroemer G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nature Reviews Molecular Cell Biology 2007; 8(9): 741-52.

Ramirez DC, Gimenez MS. Induction of redox changes, inducible nitric oxide synthase and cyclooxygenase-2 by chronic cadmium exposure in mouse peritoneal macrophages. Toxicology Letters 2006; 145(2): 121-32.

Shintani T, Klionsky DJ. Autophagy in health and disease: a double-edged sword. Science 2004; 306(5698): 990-95.

Son YO, Lee JC, Hitron JA, Pan J, Zhang Z, Shi X. Cadmium induces intracellular ca2+- and h2o2-dependent apoptosis through jnk- and p53-mediated pathways in skin epidermal cell line. Toxicological Sciences 2010; 113(1): 127-35.

Torres M. Mitogen-activated protein kinase pathways in redox signaling. Frontiers in Bioscience 2003; 8(4): 369-91.

Wang SH, Shih YL, Ko WC, Wei YH, Shi CM. Cadmium-induced autophagy and apoptosis are mediated by a calcium signaling pathway. Cellular & Molecular Life Sciences CMLS 2008; 65(22): 3640-52.

Wang SH, Shih YL, Lee CC. The role of endoplasmic reticulum in cadmium-induced mesangial cell apoptosis. Chemico-Biological Interactions 2009; 181(1): 45-51.

Yang LY, Wu KH, Chiu WT, Wang SH, Shih CM. The cadmium-induced death of mesangial cells results in nephrotoxicity. Autophagy 2009; 5(4): 571-72.

Yuan Y, Jiang C, Hu F, Wang Q, Zhang K, Wang Y, Gu J, Liu X, Bian J, Liu Z. The role of mitogen-activated protein kinase in cadmium-induced primary rat cerebral cortical neurons apoptosis via a mitochondrial apoptotic pathway. Journal of Trace Elements in Medicine and Biology 2015; 29:275-83.

Supporting Agencies

| NeuroScience + QuantumPhysics> NeuroQuantology :: Copyright 2001-2019