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Mfn2-Mediated Preservation of Mitochondrial Function Contributes to the Protective Effects of BHAPI in Response to Ischemia

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Abstract

Disturbances in intracellular iron homeostasis are associated with neuronal injury after stroke. However, exposure of cells to classical chelators may interfere with physiological iron functions. BHAPI is an iron prochelator that exerts strong iron binding capacity only under oxidative stress conditions. This study investigated the protective effects of N′-(1-(2-((4-(4,4,5,5-tetramethyl-1,2,3-dioxoborolan-2-yl)benzyl)oxy)phenyl)ethylidene (BHAPI) on an in vitro ischemia model mimicked by oxygen and glucose deprivation (OGD) in neuronal HT22 cells. The results showed that BHAPI significantly increased cell viability and decreased lactate dehydrogenase (LDH) release after OGD. BHAPI treatment also reduced apoptosis, as measured by flow cytometry, and suppressed caspase-3 activation. These protective effects were accompanied by preserved mitochondrial membrane potential (MMP), reduced mitochondrial swelling, promoted mitochondrial calcium buffering capacity, and increased mitochondrial respiration. The results of MitoTracker staining showed that BHAPI partially prevented the OGD-induced changes in mitochondrial morphology. Furthermore, BHAPI selectively increased the expression of mitochondrial dynamic protein Mfn2, with no effect on Mfn1 expression. Knockdown of Mfn2 with specific siRNA partially reversed the protective effects of BHAPI. In summary, the iron prochelator BHAPI protects HT22 cells against ischemic injury through preservation of mitochondrial function and Mfn2 signaling.

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Authors and Affiliations

  1. Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi’an City, Shaanxi Province, 710038, China

    Xiao-Li Chen, Jia-Qi Ding, Jia-Ji Lin & Zhu-Yi Li

  2. Department of Neurology, Shaanxi Provincial People’s Hospital, Xi’an City, Shaanxi Province, 710068, China

    Xiao-Li Chen, Sheng-Long Guo & Qian Yang

  3. The Department of CT, Shaanxi Provincial People’s Hospital, Xi’an City, Shaanxi Province, 710068, China

    Guo-Ping Zhang

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  1. Xiao-Li Chen
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Chen, XL., Zhang, GP., Guo, SL. et al. Mfn2-Mediated Preservation of Mitochondrial Function Contributes to the Protective Effects of BHAPI in Response to Ischemia. J Mol Neurosci 63, 267–274 (2017). https://doi.org/10.1007/s12031-017-0976-z

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  • DOI: https://doi.org/10.1007/s12031-017-0976-z

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