Open Access

Overexpression of mitochondrial Hsp75 protects neural stem cells against microglia-derived soluble factor-induced neurotoxicity by regulating mitochondrial permeability transition pore opening in vitro

  • Authors:
    • Yan Wang
    • Jizong Lin
    • Qing-Zhuang Chen
    • Ning Zhu
    • De-Qi Jiang
    • Ming-Xing Li
    • Yong Wang
  • View Affiliations

  • Published online on: October 19, 2015     https://doi.org/10.3892/ijmm.2015.2380
  • Pages: 1487-1496
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Microglia (MG)-induced neurotoxicity, a major determinant of Alzheimer's disease, is closely related to the survival of neural stem cells (NSCs). Heat shock protein 75 (Hsp75) has been reported to exert protective effects against environmental stresses; however, whether or not it protects NSCs against MG-derived soluble factor-induced neurotoxicity remains unclear. In the present study, we constructed NSCs that overexpressed human Hsp75 protein and established a co-culture system in order to elucidate the role of Hsp75 in NSC-MG interactions. The results obtained indicated that Hsp75 expression increased after 12 h of soluble factor induction and continued to increase for up to 36 h of treatment. The overexpression of Hsp75 decreased NSC apoptosis and preserved mitochondrial membrane potential. Further experiments revealed that the overexpression of Hsp75 inhibited the formation of cyclophilin D (CypD)-dependent mitochondrial permeability transition pore (mPTP) involvement in neurotoxicity-mediated mitochondrial dysfunction and suppressed the activation of the mitochondrial apoptotic cascade, as demonstrated by the inhibition of the release of cytochrome c (Cytc) and the activation of caspase-3. The findings of this study demonstrate that Hsp75 overexpression prevents the impairment of NSCs induced by MG-derived soluble factors by regulating the opening of mPTP. Thus, Hsp75 warrants further investigation as a potential candidate for protection against neurotoxicity.
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December-2015
Volume 36 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Wang Y, Lin J, Chen Q, Zhu N, Jiang D, Li M and Wang Y: Overexpression of mitochondrial Hsp75 protects neural stem cells against microglia-derived soluble factor-induced neurotoxicity by regulating mitochondrial permeability transition pore opening in vitro. Int J Mol Med 36: 1487-1496, 2015
APA
Wang, Y., Lin, J., Chen, Q., Zhu, N., Jiang, D., Li, M., & Wang, Y. (2015). Overexpression of mitochondrial Hsp75 protects neural stem cells against microglia-derived soluble factor-induced neurotoxicity by regulating mitochondrial permeability transition pore opening in vitro. International Journal of Molecular Medicine, 36, 1487-1496. https://doi.org/10.3892/ijmm.2015.2380
MLA
Wang, Y., Lin, J., Chen, Q., Zhu, N., Jiang, D., Li, M., Wang, Y."Overexpression of mitochondrial Hsp75 protects neural stem cells against microglia-derived soluble factor-induced neurotoxicity by regulating mitochondrial permeability transition pore opening in vitro". International Journal of Molecular Medicine 36.6 (2015): 1487-1496.
Chicago
Wang, Y., Lin, J., Chen, Q., Zhu, N., Jiang, D., Li, M., Wang, Y."Overexpression of mitochondrial Hsp75 protects neural stem cells against microglia-derived soluble factor-induced neurotoxicity by regulating mitochondrial permeability transition pore opening in vitro". International Journal of Molecular Medicine 36, no. 6 (2015): 1487-1496. https://doi.org/10.3892/ijmm.2015.2380