Distinct Signaling Pathways for Autophagy-Driven Cell Death and Survival in Adult Hippocampal Neural Stem Cells

Autophagy is a cellular catabolic process that degrades and recycles cellular materials. Autophagy is considered to be beneficial to the cell and organism by preventing the accumulation of toxic protein aggregates, removing damaged organelles, and providing bioenergetic substrates that are necessary...

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Main Authors: Seol-Hwa Jeong, Hyun-Kyu An, Shinwon Ha, Seong-Woon Yu
Format: Article
Language:English
Published: MDPI AG 2023-05-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/9/8289
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author Seol-Hwa Jeong
Hyun-Kyu An
Shinwon Ha
Seong-Woon Yu
author_facet Seol-Hwa Jeong
Hyun-Kyu An
Shinwon Ha
Seong-Woon Yu
author_sort Seol-Hwa Jeong
collection DOAJ
description Autophagy is a cellular catabolic process that degrades and recycles cellular materials. Autophagy is considered to be beneficial to the cell and organism by preventing the accumulation of toxic protein aggregates, removing damaged organelles, and providing bioenergetic substrates that are necessary for survival. However, autophagy can also cause cell death depending on cellular contexts. Yet, little is known about the signaling pathways that differentially regulate the opposite outcomes of autophagy. We have previously reported that insulin withdrawal (IW) or corticosterone (CORT) induces autophagic cell death (ACD) in adult hippocampal neural stem (HCN) cells. On the other hand, metabolic stresses caused by 2-deoxy-D-glucose (2DG) and glucose-low (GL) induce autophagy without death in HCN cells. Rather, we found that 2DG-induced autophagy was cytoprotective. By comparing IW and CORT conditions with 2DG treatment, we revealed that ERK and JNK are involved with 2DG-induced protective autophagy, whereas GSK-3β regulates death-inducing autophagy. These data suggest that cell death and survival-promoting autophagy undergo differential regulation with distinct signaling pathways in HCN cells.
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spelling doaj.art-cdb5cac2582d436b810eb027de9a375b2023-11-17T23:07:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-01249828910.3390/ijms24098289Distinct Signaling Pathways for Autophagy-Driven Cell Death and Survival in Adult Hippocampal Neural Stem CellsSeol-Hwa Jeong0Hyun-Kyu An1Shinwon Ha2Seong-Woon Yu3Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of KoreaDepartment of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of KoreaDepartment of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of KoreaDepartment of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of KoreaAutophagy is a cellular catabolic process that degrades and recycles cellular materials. Autophagy is considered to be beneficial to the cell and organism by preventing the accumulation of toxic protein aggregates, removing damaged organelles, and providing bioenergetic substrates that are necessary for survival. However, autophagy can also cause cell death depending on cellular contexts. Yet, little is known about the signaling pathways that differentially regulate the opposite outcomes of autophagy. We have previously reported that insulin withdrawal (IW) or corticosterone (CORT) induces autophagic cell death (ACD) in adult hippocampal neural stem (HCN) cells. On the other hand, metabolic stresses caused by 2-deoxy-D-glucose (2DG) and glucose-low (GL) induce autophagy without death in HCN cells. Rather, we found that 2DG-induced autophagy was cytoprotective. By comparing IW and CORT conditions with 2DG treatment, we revealed that ERK and JNK are involved with 2DG-induced protective autophagy, whereas GSK-3β regulates death-inducing autophagy. These data suggest that cell death and survival-promoting autophagy undergo differential regulation with distinct signaling pathways in HCN cells.https://www.mdpi.com/1422-0067/24/9/8289autophagyautophagic cell deathERKJNKGSK-3βadult hippocampal neural stem cells
spellingShingle Seol-Hwa Jeong
Hyun-Kyu An
Shinwon Ha
Seong-Woon Yu
Distinct Signaling Pathways for Autophagy-Driven Cell Death and Survival in Adult Hippocampal Neural Stem Cells
International Journal of Molecular Sciences
autophagy
autophagic cell death
ERK
JNK
GSK-3β
adult hippocampal neural stem cells
title Distinct Signaling Pathways for Autophagy-Driven Cell Death and Survival in Adult Hippocampal Neural Stem Cells
title_full Distinct Signaling Pathways for Autophagy-Driven Cell Death and Survival in Adult Hippocampal Neural Stem Cells
title_fullStr Distinct Signaling Pathways for Autophagy-Driven Cell Death and Survival in Adult Hippocampal Neural Stem Cells
title_full_unstemmed Distinct Signaling Pathways for Autophagy-Driven Cell Death and Survival in Adult Hippocampal Neural Stem Cells
title_short Distinct Signaling Pathways for Autophagy-Driven Cell Death and Survival in Adult Hippocampal Neural Stem Cells
title_sort distinct signaling pathways for autophagy driven cell death and survival in adult hippocampal neural stem cells
topic autophagy
autophagic cell death
ERK
JNK
GSK-3β
adult hippocampal neural stem cells
url https://www.mdpi.com/1422-0067/24/9/8289
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AT hyunkyuan distinctsignalingpathwaysforautophagydrivencelldeathandsurvivalinadulthippocampalneuralstemcells
AT shinwonha distinctsignalingpathwaysforautophagydrivencelldeathandsurvivalinadulthippocampalneuralstemcells
AT seongwoonyu distinctsignalingpathwaysforautophagydrivencelldeathandsurvivalinadulthippocampalneuralstemcells