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Phenoxythiophene sulfonamide compound B355252 protects neuronal cells against glutamate‑induced excitotoxicity by attenuating mitochondrial fission and the nuclear translocation of AIF

  • Authors:
    • Yuxin Zhang
    • Nailya S. Gliyazova
    • P. Andy Li
    • Gordon Ibeanu
  • View Affiliations

  • Published online on: January 18, 2021     https://doi.org/10.3892/etm.2021.9652
  • Article Number: 221
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Glutamate neurotoxicity has been implicated in the initiation and progression of various neurological and neurodegenerative disorders. Therefore, it is necessary to develop therapeutics for the treatment of patients with these devastating diseases. Mitochondrial fission plays an import role in the mediation of cell death and survival. The objective of the present study was to determine whether B355252, a phenoxythiophene sulfonamide derivative, reduces glutamate‑­induced cell death by inhibiting mitochondrial fission and the nuclear translocation of apoptosis‑inducing factor (AIF) in glutamate‑challenged HT22 neuronal cells. The results revealed that glutamate treatment led to large increases in the mitochondrial levels of the major fission proteins dynamin‑related protein 1 (Drp1) and mitochondrial fission 1 protein (Fis1), but only small elevations in the fusion proteins mitofusin 1 and 2 (Mfn1/2) and optic atrophy 1 (Opa1). In addition, glutamate toxicity disrupted mitochondrial reticular networks and increased the translocation of AIF to the nucleus. Pretreatment with B35525 reduced glutamate‑induced cell death and prevented the increases in the protein levels of Drp1, Fis1, Mfn1/2 and Opa1 in the mitochondrial fraction. More importantly, the architecture of the mitochondria was protected and nuclear translocation of AIF was completely inhibited by B35525. These findings suggest that the regulation of mitochondrial dynamics is central to the neuroprotective properties of B355252, and presents an attractive opportunity for potential development as a therapy for neurodegenerative disorders associated with mitochondria dysfunction.
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March-2021
Volume 21 Issue 3

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Zhang Y, Gliyazova NS, Li P and Ibeanu G: Phenoxythiophene sulfonamide compound B355252 protects neuronal cells against glutamate‑induced excitotoxicity by attenuating mitochondrial fission and the nuclear translocation of AIF. Exp Ther Med 21: 221, 2021
APA
Zhang, Y., Gliyazova, N.S., Li, P., & Ibeanu, G. (2021). Phenoxythiophene sulfonamide compound B355252 protects neuronal cells against glutamate‑induced excitotoxicity by attenuating mitochondrial fission and the nuclear translocation of AIF. Experimental and Therapeutic Medicine, 21, 221. https://doi.org/10.3892/etm.2021.9652
MLA
Zhang, Y., Gliyazova, N. S., Li, P., Ibeanu, G."Phenoxythiophene sulfonamide compound B355252 protects neuronal cells against glutamate‑induced excitotoxicity by attenuating mitochondrial fission and the nuclear translocation of AIF". Experimental and Therapeutic Medicine 21.3 (2021): 221.
Chicago
Zhang, Y., Gliyazova, N. S., Li, P., Ibeanu, G."Phenoxythiophene sulfonamide compound B355252 protects neuronal cells against glutamate‑induced excitotoxicity by attenuating mitochondrial fission and the nuclear translocation of AIF". Experimental and Therapeutic Medicine 21, no. 3 (2021): 221. https://doi.org/10.3892/etm.2021.9652