Nickel Enhances Zinc-Induced Neuronal Cell Death by Priming the Endoplasmic Reticulum Stress Response
| Autor: | Ayane Shimizu, Masahiro Kawahara, Maho Kubota, Ken Ichiro Tanaka, Misato Kasai, Mikako Shimoda |
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| Rok vydání: | 2019 |
| Předmět: |
inorganic chemicals
Aging Programmed cell death Cell division Article Subject Carnosine medicine.disease_cause Biochemistry Cell Line chemistry.chemical_compound Nickel medicine Humans lcsh:QH573-671 Neurons Cell Death lcsh:Cytology Endoplasmic reticulum Neurotoxicity Cell Biology General Medicine medicine.disease Endoplasmic Reticulum Stress Cell biology Zinc Neuroprotective Agents chemistry Cell culture Unfolded protein response Oxidative stress Research Article |
| Zdroj: | Oxidative Medicine and Cellular Longevity Oxidative Medicine and Cellular Longevity, Vol 2019 (2019) |
| ISSN: | 1942-0994 |
| Popis: | Trace metals such as zinc (Zn), copper (Cu), and nickel (Ni) play important roles in various physiological functions such as immunity, cell division, and protein synthesis in a wide variety of species. However, excessive amounts of these trace metals cause disorders in various tissues of the central nervous system, respiratory system, and other vital organs. Our previous analysis focusing on neurotoxicity resulting from interactions between Zn and Cu revealed that Cu2+ markedly enhances Zn2+-induced neuronal cell death by activating oxidative stress and the endoplasmic reticulum (ER) stress response. However, neurotoxicity arising from interactions between zinc and metals other than copper has not been examined. Thus, in the current study, we examined the effect of Ni2+ on Zn2+-induced neurotoxicity. Initially, we found that nontoxic concentrations (0–60 μM) of Ni2+ enhance Zn2+-induced neurotoxicity in an immortalized hypothalamic neuronal cell line (GT1-7) in a dose-dependent manner. Next, we analyzed the mechanism enhancing neuronal cell death, focusing on the ER stress response. Our results revealed that Ni2+ treatment significantly primed the Zn2+-induced ER stress response, especially expression of the CCAAT-enhancer-binding protein homologous protein (CHOP). Finally, we examined the effect of carnosine (an endogenous peptide) on Ni2+/Zn2+-induced neurotoxicity and found that carnosine attenuated Ni2+/Zn2+-induced neuronal cell death and ER stress occurring before cell death. Based on our results, Ni2+ treatment significantly enhances Zn2+-induced neuronal cell death by priming the ER stress response. Thus, compounds that decrease the ER stress response, such as carnosine, may be beneficial for neurological diseases. |
| Databáze: | OpenAIRE |
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