Inhibition of histone deacetylase 6 protects hippocampal cells against mitochondria-mediated apoptosis in a model of severe oxygen-glucose deprivation

Panpan Chang, Yuzi Tian, Aaron M. Williams, Umar F. Bhatti, Baoling Liu, Yongqing Li*, Hasan B. Alam

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Background: Histone deacetylase (HDAC) 6 inhibitors have demonstrated significant protective effects in traumatic injuries. However, their roles in neuroprotection and underlying mechanisms are poorly understood. This study sought to investigate the neuroprotective effects of Tubastatin A (Tub-A), an HDAC6 inhibitor, during oxygen-glucose deprivation (OGD) in HT22 hippocampal cells. Methods: HT22 hippocampal cells were exposed to OGD. Cell viability and cytotoxicity were assessed by cell counting kit-8 (CCK-8) and lactate dehydrogenase (LDH) release assay. Cellular apoptosis was assessed by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Mitochondria membrane potential was detected using JC-1 dye. Expressions of acetylated α-tubulin, α-tubulin, cytochrome c, VDAC, Bax, Bcl-2, cleaved caspase 3, phosphorylated Akt, Akt, phosphorylated GSK3β and GSK3β were analyzed by Western blot analysis. Results: Tub-A induced acetylation of α-tubulin, demonstrating appropriate efficacy. Tub-A significantly increased cell viability and attenuated LDH release after exposure to OGD. Furthermore, Tub-A treatment blunted the increase in TUNEL-positive cells following OGD and preserved the mitochondrial membrane potential. Tub-A also attenuated the release of cytochrome c from the mitochondria into the cytoplasm and suppressed the ratio of Bax/Bcl-2 and cleaved caspase 3. This was mediated, in part, by the increased phosphorylation of Akt and GSK3β signaling pathways. Conclusion: HDAC 6 inhibition, using Tub-A, protects against OGD-induced injury in HT22 cells by modulating Akt/GSK3β signaling and inhibiting mitochondria-mediated apoptosis.

Original languageEnglish (US)
Pages (from-to)673-682
Number of pages10
JournalCurrent Molecular Medicine
Volume19
Issue number9
DOIs
StatePublished - 2019
Externally publishedYes

Keywords

  • Apoptosis
  • Histone deacetylase 6
  • HT22 cells
  • Mitochondria membrane potential
  • Neurons
  • Oxygen-glucose deprivation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology

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