TY - JOUR
T1 - Resetting Proteostasis of CIRBP with ISRIB Suppresses Neural Stem Cell Apoptosis under Hypoxic Exposure
AU - Zou, Yuankang
AU - Yuan, Ziyan
AU - Sun, Yafei
AU - Zhai, Maodeng
AU - Tan, Zhice
AU - Guan, Ruili
AU - Aschner, Michael
AU - Luo, Wenjing
AU - Zhang, Jianbin
N1 - Publisher Copyright:
© 2022 Yuankang Zou et al.
PY - 2022
Y1 - 2022
N2 - Neurological disorders are often progressive and lead to disabilities with limited available therapies. Epidemiological evidence implicated that prolonged exposure to hypoxia leads to neurological damage and a plethora of complications. Neural stem cells (NSCs) are a promising tool for neurological damage therapy in terms of their unique properties. However, the literature on the outcome of NSCs exposed to severe hypoxia is scarce. In this study, we identified a responsive gene that reacts to multiple cellular stresses, marked cold-inducible RNA-binding protein (CIRBP), which could attenuate NSC apoptosis under hypoxic pressure. Interestingly, ISRIB, a small-molecule modulator of the PERK-ATF4 signaling pathway, could prevent the reduction and apoptosis of NSCs in two steps: enhancing the expression of CIRBP through the protein kinase R- (PKR-) like endoplasmic reticulum kinase (PERK) and activating transcription factor 4 (ATF4) axis. Taken together, CIRBP was found to be a critical factor that could protect NSCs against apoptosis induced by hypoxia, and ISRIB could be acted upstream of the axis and may be recruited as an open potential therapeutic strategy to prevent or treat hypoxia-induced brain hazards.
AB - Neurological disorders are often progressive and lead to disabilities with limited available therapies. Epidemiological evidence implicated that prolonged exposure to hypoxia leads to neurological damage and a plethora of complications. Neural stem cells (NSCs) are a promising tool for neurological damage therapy in terms of their unique properties. However, the literature on the outcome of NSCs exposed to severe hypoxia is scarce. In this study, we identified a responsive gene that reacts to multiple cellular stresses, marked cold-inducible RNA-binding protein (CIRBP), which could attenuate NSC apoptosis under hypoxic pressure. Interestingly, ISRIB, a small-molecule modulator of the PERK-ATF4 signaling pathway, could prevent the reduction and apoptosis of NSCs in two steps: enhancing the expression of CIRBP through the protein kinase R- (PKR-) like endoplasmic reticulum kinase (PERK) and activating transcription factor 4 (ATF4) axis. Taken together, CIRBP was found to be a critical factor that could protect NSCs against apoptosis induced by hypoxia, and ISRIB could be acted upstream of the axis and may be recruited as an open potential therapeutic strategy to prevent or treat hypoxia-induced brain hazards.
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U2 - 10.1155/2022/3627026
DO - 10.1155/2022/3627026
M3 - Article
C2 - 36211820
AN - SCOPUS:85139415916
SN - 1942-0900
VL - 2022
JO - Oxidative Medicine and Cellular Longevity
JF - Oxidative Medicine and Cellular Longevity
M1 - 3627026
ER -