Roles of sestrin2 and ribosomal protein S6 in transient global ischemia-induced hippocampal neuronal injury

Yao Chung Chuang, Jenq Lin Yang, Ding I. Yang, Tsu Kung Lin, Chia Wei Liou, Shang Der Chen*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

33 Scopus citations


Recent studies suggested that sestrin2 is a crucial modulator for the production of reactive oxygen species (ROS). In addition, sestrin2 may also regulate ribosomal protein S6 (RpS6), a molecule important for protein synthesis, through the effect of mammalian target of rapamycin (mTOR) complex that is pivotal for longevity. However, the roles of sestrin2 in cerebral ischemia, in which oxidative stress is one of the major pathogenic mechanisms, are still less understood. In this study, we hypothesized that sestrin2 may protect hippocampal CA1 neurons against transient global ischemia (TGI)-induced apoptosis by regulating RpS6 phosphorylation in rats. We found that sestrin2 expression was progressively increased in the hippocampal CA1 subfield 1-48 h after TGI, reaching the maximal level at 24 h, and declined thereafter. Further, an increased extent of RpS6 phosphorylation, but not total RpS6 protein level, was observed in the hippocampal CA1 subfield after TGI. The sestrin2 siRNA, which substantially blocked the expression of TGI-induced sestrin2, also abolished RpS6 phosphorylation. TGI with reperfusion may induce oxidative stress with the resultant formation of 8-hydroxy-deoxyguanosine (8-OHdG). We found that sestrin2 siRNA further augmented the formation of 8-OHdG induced by TGI with reperfusion for 4 h. Consistently, sestrin2 siRNA also enhanced apoptosis induced by TGI with reperfusion for 48 h based on the analysis of DNA fragmentation by agarose gel electrophoresis, DNA fragmentation sandwich ELISA, and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Together these findings indicated that TGI-induced sestrin2 expression contributed to RpS6 phosphorylation and neuroprotection against ischemic injury in the hippocampal CA1 subfield.

Original languageEnglish
Pages (from-to)26406-26416
Number of pages11
JournalInternational Journal of Molecular Sciences
Issue number11
StatePublished - 04 11 2015

Bibliographical note

Publisher Copyright:
© 2015 by the authors; licensee MDPI, Basel, Switzerland.


  • Hippocampus CA1 neurons
  • Oxidative stress
  • Ribosomal protein S6
  • Sestrin2
  • Transient global ischemia


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