Involvement of dysregulated Wip1 in manganese-induced p53 signaling and neuronal apoptosis

Toxicology Letters
Xia MaChunhua Wan

Abstract

Overexposure to manganese (Mn) has been known to induce neuronal death and neurodegenerative symptoms. However, the precise mechanisms underlying Mn neurotoxicity remain incompletely understood. In the present study, we established a Mn-exposed rat model and found that downregulation of wild type p53-induced phosphatase 1 (Wip1) might contribute to p53 activation and resultant neuronal apoptosis following Mn exposure. Western blot and immunohistochemical analyses revealed that the expression of Wip1 was markedly decreased following Mn exposure. In addition, immunofluorescence assay demonstrated that Mn exposure led to significant reduction in the number of Wip1-positive neurons. Accordingly, the expression of Mdm2 was progressively decreased, which was accompanied with markedly increased expression of p53, as well as the ratio of Bax/Bcl-xl. Furthermore, we showed that Mn exposure decreased the viability and induced apparent apoptosis in NFG-differentiated neuron-like PC12 cells. Importantly, the expression of Wip1 decreased progressively, whereas the level of cellular p53 and the ratio of Bax/Bcl-xl were elevated, which resembled the expression of the proteins in animal model studies. Depletion of p53 significantly ameliorated...Continue Reading

References

Dec 26, 1970·Nature·B W Konigsmark, E A Murphy
Jun 10, 1997·Proceedings of the National Academy of Sciences of the United States of America·M FiscellaE Appella
Aug 30, 2002·Neurotoxicology and Teratology·Yoko Hirata
May 10, 2003·Science·Jocelyn Kaiser
May 5, 2005·Genes & Development·Xiongbin LuLawrence A Donehower
Aug 17, 2006·The Journal of Biological Chemistry·Tzippi HershkoDoron Ginsberg
Oct 16, 2007·Cancer Cell·Xiongbin LuLawrence A Donehower
Feb 13, 2008·Cancer Metastasis Reviews·Xiongbin LuLawrence A Donehower
Apr 11, 2008·Neurotoxicology·Kiran KaliaWei Zheng
Jul 18, 2009·Toxicology and Applied Pharmacology·Dejan MilatovicMichael Aschner
Mar 6, 2012·Free Radical Biology & Medicine·Cristina LanniDaniela Uberti
Apr 14, 2012·Neurotoxicology·H A RoelsMartha Maria Téllez-Rojo
May 1, 2012·Cell Cycle·Anastasia R GoloudinaOleg N Demidov
Sep 18, 2012·Journal of Theoretical Biology·Luna DimitrioRoberto Natalini
Jan 12, 2013·Cell Death and Differentiation·M KracikovaS A Aaronson
Mar 16, 2013·Journal of Molecular Neuroscience : MN·Aihong LiXingxing Gu
Oct 12, 2013·Biochimica Et Biophysica Acta·Ján EliašRoberto Natalini

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Citations

Apr 25, 2016·Neurotoxicology·Dong-Suk KimAnumantha G Kanthasamy
Nov 7, 2016·BMC Pharmacology & Toxicology·Tanara V PeresMichael Aschner
Nov 11, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Zhipeng LinRunzhou Ni
Aug 18, 2020·Expert Review of Neurotherapeutics·Airton C MartinsMichael Aschner
Dec 6, 2017·Journal of Biochemical and Molecular Toxicology·Lei WangXiaoDan Yu
Nov 21, 2019·Molecular Medicine Reports·Chang LiuYue Zhou
Apr 26, 2017·Molecular Medicine Reports·Yanping FengWei Guo
Jan 17, 2021·Stroke and Vascular Neurology·Feng YanXunming Ji
Feb 24, 2021·Expert Opinion on Drug Metabolism & Toxicology·Airton C MartinsMichael Aschner
Jan 24, 2020·Neurochemistry International·Mahfuzur R MiahMichael Aschner
May 1, 2021·International Journal of Molecular Sciences·Alexey A TinkovMichael Aschner
Jun 1, 2021·Chemico-biological Interactions·Amândia R BatschauerClaudia F Ortolani-Machado

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