Alterations in histone deacetylase 2 and O-GlcNAc transferase expression following cerebral ischemia-reperfusion and the modulatory effects of zinc ions in a rat model

doi:10.3969/j.issn.1006-7795.2026.02.011

Abstract

Abstract: Objective To investigate the effect of disrupted neuronal zinc homeostasis on the expression of histone deacetylase 2 (HDAC2) and O-GlcNAc transferase (OGT), as well as their potential interaction in brain tissue following cerebral ischemia/reperfusion (I/R), in order to elucidate whether zinc dyshomeostasis participates in the synergistic epigenetic regulatory mechanisms during cerebral I/R injury. Methods Adult Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion (MCAO) for 90 min, followed by reperfusion for 6 h or 24 h. The animals were randomly divided into the Sham, MCAO, and MCAO + N,N,N′,N′-tetrakis (2-pyridylmethyl)ethylenediamine（TPEN） groups (n=6 per group). Protein expression levels of HDAC2 and OGT in brain tissue were analyzed by Western blotting. Protein-protein docking between HDAC2 and OGT was performed using the HDOCK server, and the interaction interface was visualized with PyMOL. Results ①Compared with the Sham group, HDAC2 protein expression in rat ischemic brain tissue was significantly downregulated at 6 h and 24 h after reperfusion. ②TPEN treatment significantly upregulated HDAC2 expression in rat ischemic brain tissue at both 6 h and 24 h after reperfusion.③Compared with the Sham group, OGT protein expression in rat ischemic brain tissue was markedly reduced at 24 h after reperfusion.④TPEN treatment significantly increased OGT expression in rat ischemic brain tissue at both 6 h and 24 h after reperfusion. ⑤ Molecular docking analysis revealed high-confidence binding conformations between HDAC2 and OGT, suggesting a potential protein-protein interaction based on structural complementarity. Conclusion Cerebral ischemia-reperfusion leads to a marked downregulation of HDAC2 and OGT expression in rat ischemic brain tissue, which is closely associated with excessive zinc accumulation. The potential protein-protein interaction between OGT and HDAC2 further suggests that zinc overload after ischemia may simultaneously alter their expression levels and disrupt their interaction, thereby impairing neuronal epigenetic regulatory processes.

Key words: cerebral ischemia-reperfusion, zinc, histone deacetylase 2 (HDAC2), O-GlcNAc transferase (OGT), epigenetic regulation, brain injury, neuronal injury

CLC Number:

R743.3

Liu He, Zhu Yuequan, Zhou Yingnan, Bai Shangying, Zhao Haiping, Zhao Yongmei. Alterations in histone deacetylase 2 and O-GlcNAc transferase expression following cerebral ischemia-reperfusion and the modulatory effects of zinc ions in a rat model[J]. Journal of Capital Medical University, 2026, 47(2): 299-307.

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