Panpan Chang, Yuzi Tian, Aaron M. Williams, Umar F. Bhatti, Baoling Liu, Yongqing Li* and Hasan B. Alam* Pages 673 - 682 ( 10 )
<P>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 oxygenglucose deprivation (OGD) in HT22 hippocampal cells. </P><P> 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. </P><P> 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. </P><P> 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.</P>
Histone deacetylase 6, oxygen-glucose deprivation, neurons, mitochondria membrane potential, apoptosis, HT22 cells.
Department of Surgery, University of Michigan, Ann Arbor, Michigan, Department of Surgery, University of Michigan, Ann Arbor, Michigan, Department of Surgery, University of Michigan, Ann Arbor, Michigan, Department of Surgery, University of Michigan, Ann Arbor, Michigan, Department of Surgery, University of Michigan, Ann Arbor, Michigan, Department of Surgery, University of Michigan, Ann Arbor, Michigan, Department of Surgery, University of Michigan, Ann Arbor, Michigan