Publication: Cadmium induces apoptotic program imbalance and cell cycle inhibitor expression in cultured human astrocytes
Issued Date
2019-01-01
Resource Type
ISSN
18727077
13826689
13826689
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2-s2.0-85057734636
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Mahidol University
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SCOPUS
Bibliographic Citation
Environmental Toxicology and Pharmacology. Vol.65, (2019), 53-59
Suggested Citation
Dusadee Ospondpant, Suttinee Phuagkhaopong, Kran Suknuntha, Kant Sangpairoj, Thitima Kasemsuk, Chutima Srimaroeng, Pornpun Vivithanaporn Cadmium induces apoptotic program imbalance and cell cycle inhibitor expression in cultured human astrocytes. Environmental Toxicology and Pharmacology. Vol.65, (2019), 53-59. doi:10.1016/j.etap.2018.12.001 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/50945
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Title
Cadmium induces apoptotic program imbalance and cell cycle inhibitor expression in cultured human astrocytes
Abstract
© 2018 Elsevier B.V. Cadmium is a highly neurotoxic heavy metal impairing neurogenesis and induces neurodegenerative disorders. Toxic concentrations of cadmium induce astrocytic apoptosis by depleting intracellular glutathione levels, elevating intracellular calcium levels, altering mitochondria membrane potentials, and activating JNK and PI3K/Akt signaling pathways. Cadmium suppresses cell proliferation in kidney epithelial cells, lung fibroblasts, and primary myelocytes; however, cadmium's effects on proteins regulating oxidative stress, apoptosis, and cell proliferation in astrocytes are less known. The present study hypothesized that cadmium alters levels of antioxidant enzymes, apoptotic regulator proteins, and cell cycle inhibitor proteins, resulting in apoptosis and cell cycle arrest. Concentrations ≥20 μM cadmium induced apoptosis and led to intracellular changes including DNA fragmentation, reduced mRNA expression of antioxidant enzymes (i.e., catalase and glutathione S transferase-A4), downregulation of B-cell lymphoma 2 (Bcl-2), and upregulation of Bcl-2-associated X protein (Bax). Moreover, cadmium suppressed astrocytic proliferation by inducing S and G2/M phase cell cycle arrest and promoting p53, p21, and p27 expression. In conclusion, this study provides mechanistic insight into cadmium-induced cytotoxicity of astrocytes and highlights potential targets for prevention of cadmium-induced apoptosis and cell cycle arrest.