| Autor: |
Noria Okada, Tomohiro Yako, Shinsuke Nakamura, Masamitsu Shimazawa, Hideaki Hara |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Journal of Pharmacological Sciences, Vol 147, Iss 4, Pp 367-375 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
1347-8613 |
| DOI: |
10.1016/j.jphs.2021.09.001 |
| Popis: |
Huntington's disease (HD) is an inherited neurodegenerative disorder caused by CAG repeat expansion in the huntingtin (HTT) gene. Here, we examined the effects of antioxidants on 3-nitropropionic acid (3-NP; a mitochondrial complex II inhibitor)-induced mitochondrial dysfunction and cell death in STHdhQ111 striatal cells carrying homozygous mutant HTT with extended CAG repeats compared with those in STHdhQ7 striatal cells. 3-NP reduced cell viability and increased cell death both in STHdhQ111 and STHdhQ7, and the cytotoxicity was markedly attenuated by antioxidants (N-acetyl-l-cysteine and edaravone). Furthermore, 3-NP increased intracellular reactive oxygen species (ROS) production in both cell lines, and this increase was inhibited by antioxidants. Mitochondrial ROS was also increased by 3-NP in STHdhQ111 but not in STHdhQ7, and this increase was significantly inhibited by edaravone. Mitochondrial membrane potential (MMP) was lower in STHdhQ111 than that in STHdhQ7, and antioxidants prevented 3-NP-induced MMP decrease in STHdhQ111.3-NP enhanced oligomerization of dynamin-related protein 1 (Drp1), a protein that promotes mitochondrial fission in both cells, and both antioxidants prevented the increase in oligomerization. These results suggest that reduced mitochondrial complex II activity enhances cell death via intracellular ROS production and Drp1 oligomerization in striatal cells with mutant HTT and antioxidants may reduce striatal cell death. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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