Butyrate Ameliorates Mitochondrial Respiratory Capacity of The Motor-Neuron-like Cell Line NSC34-G93A, a Cellular Model for ALS
Mitochondrial defects in motor neurons are pathological hallmarks of ALS, a neuromuscular disease with no effective treatment. Studies have shown that butyrate, a natural gut-bacteria product, alleviates the disease progression of ALS mice overexpressing a human ALS-associated mutation, hSOD1<sup...
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MDPI AG
2022-02-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/2/333 |
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| author | Xuejun Li Li Dong Ang Li Jianxun Yi Marco Brotto Jingsong Zhou |
| author_facet | Xuejun Li Li Dong Ang Li Jianxun Yi Marco Brotto Jingsong Zhou |
| author_sort | Xuejun Li |
| collection | DOAJ |
| description | Mitochondrial defects in motor neurons are pathological hallmarks of ALS, a neuromuscular disease with no effective treatment. Studies have shown that butyrate, a natural gut-bacteria product, alleviates the disease progression of ALS mice overexpressing a human ALS-associated mutation, hSOD1<sup>G93A</sup>. In the current study, we examined the potential molecular mechanisms underlying the effect of butyrate on mitochondrial function in cultured motor-neuron-like NSC34 with overexpression of hSOD1<sup>G93A</sup> (NSC34-G93A). The live cell confocal imaging study demonstrated that 1mM butyrate in the culture medium improved the mitochondrial network with reduced fragmentation in NSC34-G93A cells. Seahorse analysis revealed that NSC34-G93A cells treated with butyrate showed an increase of ~5-fold in mitochondrial Spare Respiratory Capacity with elevated Maximal Respiration. The time-dependent changes in the mRNA level of PGC1α, a master regulator of mitochondrial biogenesis, revealed a burst induction with an early increase (~5-fold) at 4 h, a peak at 24 h (~19-fold), and maintenance at 48 h (8-fold) post-treatment. In line with the transcriptional induction of PGC1α, both the mRNA and protein levels of the key molecules (MTCO1, MTCO2, and COX4) related to the mitochondrial electron transport chain were increased following the butyrate treatment. Our data indicate that activation of the PGC1α signaling axis could be one of the molecular mechanisms underlying the beneficial effects of butyrate treatment in improving mitochondrial bioenergetics in NSC34-G93A cells. |
| first_indexed | 2024-03-09T22:28:43Z |
| format | Article |
| id | doaj.art-2f88051c33e14783a716e55faf0624da |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T22:28:43Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-2f88051c33e14783a716e55faf0624da2023-11-23T19:00:15ZengMDPI AGBiomolecules2218-273X2022-02-0112233310.3390/biom12020333Butyrate Ameliorates Mitochondrial Respiratory Capacity of The Motor-Neuron-like Cell Line NSC34-G93A, a Cellular Model for ALSXuejun Li0Li Dong1Ang Li2Jianxun Yi3Marco Brotto4Jingsong Zhou5Department of Kinesiology, College of Nursing and Health Innovation, University of Texas at Arlington, Arlington, TX 76019, USADepartment of Kinesiology, College of Nursing and Health Innovation, University of Texas at Arlington, Arlington, TX 76019, USADepartment of Kinesiology, College of Nursing and Health Innovation, University of Texas at Arlington, Arlington, TX 76019, USADepartment of Kinesiology, College of Nursing and Health Innovation, University of Texas at Arlington, Arlington, TX 76019, USABone-Muscle Research Center, College of Nursing and Health Innovation, University of Texas at Arlington, Arlington, TX 76019, USADepartment of Kinesiology, College of Nursing and Health Innovation, University of Texas at Arlington, Arlington, TX 76019, USAMitochondrial defects in motor neurons are pathological hallmarks of ALS, a neuromuscular disease with no effective treatment. Studies have shown that butyrate, a natural gut-bacteria product, alleviates the disease progression of ALS mice overexpressing a human ALS-associated mutation, hSOD1<sup>G93A</sup>. In the current study, we examined the potential molecular mechanisms underlying the effect of butyrate on mitochondrial function in cultured motor-neuron-like NSC34 with overexpression of hSOD1<sup>G93A</sup> (NSC34-G93A). The live cell confocal imaging study demonstrated that 1mM butyrate in the culture medium improved the mitochondrial network with reduced fragmentation in NSC34-G93A cells. Seahorse analysis revealed that NSC34-G93A cells treated with butyrate showed an increase of ~5-fold in mitochondrial Spare Respiratory Capacity with elevated Maximal Respiration. The time-dependent changes in the mRNA level of PGC1α, a master regulator of mitochondrial biogenesis, revealed a burst induction with an early increase (~5-fold) at 4 h, a peak at 24 h (~19-fold), and maintenance at 48 h (8-fold) post-treatment. In line with the transcriptional induction of PGC1α, both the mRNA and protein levels of the key molecules (MTCO1, MTCO2, and COX4) related to the mitochondrial electron transport chain were increased following the butyrate treatment. Our data indicate that activation of the PGC1α signaling axis could be one of the molecular mechanisms underlying the beneficial effects of butyrate treatment in improving mitochondrial bioenergetics in NSC34-G93A cells.https://www.mdpi.com/2218-273X/12/2/333butyratePGC1αmitochondriaNSC34 cell lineALS |
| spellingShingle | Xuejun Li Li Dong Ang Li Jianxun Yi Marco Brotto Jingsong Zhou Butyrate Ameliorates Mitochondrial Respiratory Capacity of The Motor-Neuron-like Cell Line NSC34-G93A, a Cellular Model for ALS Biomolecules butyrate PGC1α mitochondria NSC34 cell line ALS |
| title | Butyrate Ameliorates Mitochondrial Respiratory Capacity of The Motor-Neuron-like Cell Line NSC34-G93A, a Cellular Model for ALS |
| title_full | Butyrate Ameliorates Mitochondrial Respiratory Capacity of The Motor-Neuron-like Cell Line NSC34-G93A, a Cellular Model for ALS |
| title_fullStr | Butyrate Ameliorates Mitochondrial Respiratory Capacity of The Motor-Neuron-like Cell Line NSC34-G93A, a Cellular Model for ALS |
| title_full_unstemmed | Butyrate Ameliorates Mitochondrial Respiratory Capacity of The Motor-Neuron-like Cell Line NSC34-G93A, a Cellular Model for ALS |
| title_short | Butyrate Ameliorates Mitochondrial Respiratory Capacity of The Motor-Neuron-like Cell Line NSC34-G93A, a Cellular Model for ALS |
| title_sort | butyrate ameliorates mitochondrial respiratory capacity of the motor neuron like cell line nsc34 g93a a cellular model for als |
| topic | butyrate PGC1α mitochondria NSC34 cell line ALS |
| url | https://www.mdpi.com/2218-273X/12/2/333 |
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