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FTO knockdown alleviates hypoxia-induced PC12 cell injury by stabilizing GADD45B in an IGF2BP2-dependent manner.

Abstract
RNA N6-methyladenosine (m6A) level is closely associated with neurodevelopment and central nervous system dysfunctions including spinal cord injury (SCI). M6A level can be dynamically regulated by m6A methyltransferases and demethylases. In this text, the roles of m6A demethylase FTO alpha-ketoglutarate dependent dioxygenase (FTO) in SCI development along with its m6A-dependent regulatory mechanisms were investigated in hypoxia-induced PC12 cell injury model. The results showed that FTO was low expressed in spinal cord tissues of rats after contusive SCI and hypoxia-treated PC12 cells. FTO knockdown alleviated hypoxia-induced PC12 cell injury. FTO loss increased GADD45B expression and m6A level in PC12 cells. GADD45B knockdown weakened the protective effects of FTO depletion on hypoxia-treated PC12 cells. FTO regulated GADD45B expression in an IGF2BP2-dependent manner. In conclusion, FTO knockdown mitigated the injury of hypoxia-induced PC12 cells by up-regulating GADD45B in an IGF2BP2-dependent manner.
AuthorsDan Wang, Yu Li, Xiaoxiao Xu, Shixin Zhao, Zhen Wang, Jiahao Yang, Xi Zhang, Junwei Pan, Yisheng Wang, Ming Liu
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 619 Pg. 166-172 (09 03 2022) ISSN: 1090-2104 [Electronic] United States
PMID35803057 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2022 Elsevier Inc. All rights reserved.
Chemical References
  • Antigens, Differentiation
  • Gadd45b protein, rat
  • IGF2BP2 protein, rat
  • RNA-Binding Proteins
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Ketoglutarate Dehydrogenase Complex
  • Methyltransferases
  • Adenosine
Topics
  • Adenosine (metabolism)
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO (genetics, metabolism)
  • Animals
  • Antigens, Differentiation
  • Hypoxia
  • Ketoglutarate Dehydrogenase Complex (metabolism)
  • Methyltransferases (metabolism)
  • PC12 Cells
  • RNA-Binding Proteins (metabolism)
  • Rats

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