Melatonin promotes cell cycle progression of neural stem cells subjected to manganese via Nurr1.

Publisher: John Wiley & Sons Country of Publication: United States NLM ID: 100885357 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-7278 (Electronic) Linking ISSN: 15204081 NLM ISO Abbreviation: Environ Toxicol Subsets: MEDLINE

Original Publication: New York, NY : John Wiley & Sons, c1999-

Neural Stem Cells*/drug effects ; Neural Stem Cells*/metabolism ; Melatonin*/pharmacology ; Nuclear Receptor Subfamily 4, Group A, Member 2*/metabolism ; Nuclear Receptor Subfamily 4, Group A, Member 2*/genetics ; Cell Proliferation*/drug effects ; Manganese*/toxicity ; Cell Cycle*/drug effects; Animals ; Cells, Cultured ; Mice

Excessive exposure to manganese (Mn) through drinking water and food during pregnancy significantly heightens the likelihood of neurodevelopmental damage in offspring. Multiple studies have indicated that melatonin (Mel) may help to relieve neurodevelopmental disorders caused by Mn, but potential mechanisms underlying this effect require further exploration. Here, we utilized primary neural stem cells (NSCs) as a model to elucidate the molecular mechanism underlying the protective function of Mel on Mn-induced cell proliferation dysfunction and cycle arrest. Our results showed that Mn disrupted the cell cycle in NSCs by suppressing positive regulatory proteins (CDK2, Cyclin A, Cyclin D 1 , and E2F1) and enhancing negative ones (p27 ^KIP1 and p57 ^KIP2 ), leading to cell proliferation dysfunction. Mel inhibited the Mn-dependent changes to these proteins and the cell cycle through nuclear receptor-related protein 1 (Nurr1), thus alleviating the proliferation dysfunction. Knockdown of Nurr1 using lentivirus-expressed shRNA in NSCs resulted in a diminished protective effect of Mel. We concluded that Mel mitigated Mn-induced proliferation dysfunction and cycle arrest in NSCs through Nurr1.
(© 2024 Wiley Periodicals LLC.)

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Keywords: cell cycle; manganese; melatonin; neural stem cells; nuclear receptor‐related protein 1

JL5DK93RCL (Melatonin)
0 (Nuclear Receptor Subfamily 4, Group A, Member 2)
42Z2K6ZL8P (Manganese)
0 (Nr4a2 protein, mouse)

Date Created: 20240402 Date Completed: 20240611 Latest Revision: 20240621

20240621

10.1002/tox.24258

38563506