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Metabolic Regulation of Hippocampal Neuroprogenitor Apoptosis After Irradiation.

Abstract

The tumor suppressor p53 is an important regulator of cell fate response after DNA damage. Cell fate response following metabolic stresses has also been linked to p53-dependent pathways. In this study, we asked if 5'-adenosine monophosphate-activated protein kinase (AMPK), the master sensor of cellular energy balance, played a role in p53-dependent apoptosis of neural progenitor cells (NPCs) in the hippocampus after irradiation. Adult mice with targeted disruption of p53 or prkaa2 (gene that encodes AMPKα) in the brain were used to determine the role of p53 and AMPK, respectively, in radiation-induced apoptosis of NPCs in the hippocampus. The p53-dependent apoptosis of NPCs was associated with an increase in phospho-AMPK expression in the dentate gyrus at 8 hours after irradiation. Activation of AMPK was seen in granule neurons and subgranular NPCs. Compared with wildtype mice, apoptosis of NPCs was significantly attenuated in AMPK deficient (nestinCre: prkaa2fl/fl) mice after irradiation. AMPK deficiency did not however alter p53 activation in NPCs after irradiation. We conclude that AMPK may regulate apoptosis of hippocampal NPCs after irradiation. These findings suggest that cellular metabolism may play a role in determining cell fate response such as apoptosis after DNA damage in NPCs.

Authors+Show Affiliations

Sunnybrook Health Sciences Centre.University Health Network. Departments of Radiation Oncology and Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.Sunnybrook Health Sciences Centre. Departments of Radiation Oncology and Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31738417

Citation

Li, Yu-Qing, et al. "Metabolic Regulation of Hippocampal Neuroprogenitor Apoptosis After Irradiation." Journal of Neuropathology and Experimental Neurology, 2019.
Li YQ, Koritzinsky M, Wong CS. Metabolic Regulation of Hippocampal Neuroprogenitor Apoptosis After Irradiation. J Neuropathol Exp Neurol. 2019.
Li, Y. Q., Koritzinsky, M., & Wong, C. S. (2019). Metabolic Regulation of Hippocampal Neuroprogenitor Apoptosis After Irradiation. Journal of Neuropathology and Experimental Neurology, doi:10.1093/jnen/nlz108.
Li YQ, Koritzinsky M, Wong CS. Metabolic Regulation of Hippocampal Neuroprogenitor Apoptosis After Irradiation. J Neuropathol Exp Neurol. 2019 Oct 19; PubMed PMID: 31738417.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metabolic Regulation of Hippocampal Neuroprogenitor Apoptosis After Irradiation. AU - Li,Yu-Qing, AU - Koritzinsky,Marianne, AU - Wong,C Shun, Y1 - 2019/10/19/ PY - 2019/08/06/received PY - 2019/09/23/revised PY - 2019/11/19/entrez KW - AMPK KW - Apoptosis KW - Hippocampus KW - Irradiation KW - Neuroprogenitors KW - p53 JF - Journal of neuropathology and experimental neurology JO - J. Neuropathol. Exp. Neurol. N2 - The tumor suppressor p53 is an important regulator of cell fate response after DNA damage. Cell fate response following metabolic stresses has also been linked to p53-dependent pathways. In this study, we asked if 5'-adenosine monophosphate-activated protein kinase (AMPK), the master sensor of cellular energy balance, played a role in p53-dependent apoptosis of neural progenitor cells (NPCs) in the hippocampus after irradiation. Adult mice with targeted disruption of p53 or prkaa2 (gene that encodes AMPKα) in the brain were used to determine the role of p53 and AMPK, respectively, in radiation-induced apoptosis of NPCs in the hippocampus. The p53-dependent apoptosis of NPCs was associated with an increase in phospho-AMPK expression in the dentate gyrus at 8 hours after irradiation. Activation of AMPK was seen in granule neurons and subgranular NPCs. Compared with wildtype mice, apoptosis of NPCs was significantly attenuated in AMPK deficient (nestinCre: prkaa2fl/fl) mice after irradiation. AMPK deficiency did not however alter p53 activation in NPCs after irradiation. We conclude that AMPK may regulate apoptosis of hippocampal NPCs after irradiation. These findings suggest that cellular metabolism may play a role in determining cell fate response such as apoptosis after DNA damage in NPCs. SN - 1554-6578 UR - https://www.unboundmedicine.com/medline/citation/31738417/Metabolic_Regulation_of_Hippocampal_Neuroprogenitor_Apoptosis_After_Irradiation L2 - https://academic.oup.com/jnen/article-lookup/doi/10.1093/jnen/nlz108 DB - PRIME DP - Unbound Medicine ER -