4.7 Article

PINK1/Parkin-mediated mitophagy modulates cadmium-induced apoptosis in rat cerebral cortical neurons

Journal

ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
Volume 244, Issue -, Pages -

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ecoenv.2022.114052

Keywords

Cadmium; Rat cerebral cortical neuron; PINK1; Parkin pathway; Mitophagy; Apoptosis

Funding

  1. National Natural Science Foundation of China
  2. Natural Science Foundation of Jiangsu Province
  3. Postgraduate Research & Practice Innovation Program of Jiangsu Province
  4. Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
  5. [31772808]
  6. [31872533]
  7. [BK20221372]
  8. [SJCX21_1634]

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Cadmium is an environmental pollutant with neurotoxicity. This study found that mitochondrial dysfunction leads to mitophagy and apoptosis, while inhibiting cyclosporine A exacerbates cell apoptosis. Similar results were observed in in vivo experiments. The study suggests that PINK1/Parkin-mediated mitophagy plays an important role in neuroprotection.
Cadmium is a persistent environmental pollutant whose neurotoxicity is of serious concern. Mitochondrial dysfunction and its mediated mitophagy and apoptosis are considered key events in Cd-induced neurological pathologies, but the exact molecular mechanism has not been fully elucidated. The aim of this study was to investigate the relationship between Cd-induced mitophagy and apoptosis and their role in Cd-induced neuronal death. Using the mitophagy inhibitor cyclosporine A (CsA), we found that the extent of mitophagy mediated by the PTEN-induced putative kinase protein 1 (PINK1)/E3 ubiquitin ligase (Parkin) pathway decreased, whereas the level of apoptosis and cell death increased in rat cerebral cortical neurons in vitro. Consistent with this, the knockdown of PINK1 also exacerbated Cd-induced apoptosis and neuronal death. Furthermore, the results of the in vivo experiments showed that Cd simultaneously activated both mitophagy and apoptosis and that the sup-pression of mitophagy by CsA aggravated Cd-induced apoptosis. In summary, our results indicate that PINK1/ Parkin-mediated mitophagy exerts an important neuroprotective effect by inhibiting Cd-mediated apoptosis in rat cerebral cortical neurons both in vitro and in vivo. This work may allow the development of new therapeutic strategies for Cd-induced central nervous system disorders.

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