Morphological control of mitochondria as the novel mechanism of Gastrodia elata in attenuating mutant huntingtin-induced protein aggregations

Nai Kuei Huang, Chung Chih Lin, Yun Lian Lin, Chuen Lin Huang, Chun Tang Chiou, Yi Chao Lee, Shu Yi Lee, Hung Tse Huang, Ying Chen Yang

研究成果: 雜誌貢獻文章

摘要

Background: According to Compendium of Materia Medica, Gastrodia elata (GE) Blume as a top grade and frequently prescribed herbal medicine has been used in treating dizziness, headaches, and epilepsy, indicating a neuroprotective effect. Because GE is capable of suppressing a hyperactive liver and thus calming endogenous wind, and because Huntington's disease (HD) can be classified as a phenomenon of disturbed liver wind, it is suggested that GE might be beneficial in treating HD. However, although current studies support GE for the prevention of diverse neurodegenerations such as HD, its detailed mechanisms remain elusive. Purpose: To investigate the molecular mechanism of GE in preventing HD by focusing on mitochondrial morphology, which is highly associated with HD etiology and thus proposed as a therapeutic target of neurodegenerations. Study design/methods: The overexpression of the mutant huntingtin (mHTT) gene in rat pheochromocytoma (PC12) cells was used as an in vitro cell model of HD. A filter retardation assay was applied to measure protein aggregations during HTT expression. Cotransfection with mitochondrial fusion and fission genes was used to test their relationships with HTT aggregates by monitoring with a confocal laser scanning microscope and filter retardation assay. Western blot analysis was used to estimate protein expression under different drug treatments or cotransfections with other related genes. Results: The overexpression of mutant but not normal HTT genes significantly resulted in protein aggregations in PC12 cells. GE dose-dependently attenuated mHTT-induced protein aggregations and free radical formations. GE significantly reversed mHTT-induced mitochondrial fragmentation and dysregulation of mitochondrial fusion and fission molecules. The overexpression of mitochondrial fusion genes attenuated mHTT-induced protein aggregations. Further, Mdivi-1, a DRP1 fission molecule inhibitor, significantly reversed mHTT-induced protein aggregations and mitochondrial fragmentation. Conclusion: GE attenuated mHTT aggregations through the control of mitochondrial fusion and the fission pathway.
原文英語
文章編號152756
期刊Phytomedicine
59
DOIs
出版狀態已發佈 - 六月 1 2019

指紋

Gastrodia
Mutant Proteins
Huntington Disease
Mitochondria
Mitochondrial Dynamics
PC12 Cells
Genes
Materia Medica
Proteins
Mitochondrial Genes
Huntingtin Protein
Herbal Medicine
Liver
Dizziness
Pheochromocytoma
Neuroprotective Agents
Free Radicals
Headache
Epilepsy
Lasers

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine

引用此文

Morphological control of mitochondria as the novel mechanism of Gastrodia elata in attenuating mutant huntingtin-induced protein aggregations. / Huang, Nai Kuei; Lin, Chung Chih; Lin, Yun Lian; Huang, Chuen Lin; Chiou, Chun Tang; Lee, Yi Chao; Lee, Shu Yi; Huang, Hung Tse; Yang, Ying Chen.

於: Phytomedicine, 卷 59, 152756, 01.06.2019.

研究成果: 雜誌貢獻文章

Huang, Nai Kuei ; Lin, Chung Chih ; Lin, Yun Lian ; Huang, Chuen Lin ; Chiou, Chun Tang ; Lee, Yi Chao ; Lee, Shu Yi ; Huang, Hung Tse ; Yang, Ying Chen. / Morphological control of mitochondria as the novel mechanism of Gastrodia elata in attenuating mutant huntingtin-induced protein aggregations. 於: Phytomedicine. 2019 ; 卷 59.
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abstract = "Background: According to Compendium of Materia Medica, Gastrodia elata (GE) Blume as a top grade and frequently prescribed herbal medicine has been used in treating dizziness, headaches, and epilepsy, indicating a neuroprotective effect. Because GE is capable of suppressing a hyperactive liver and thus calming endogenous wind, and because Huntington's disease (HD) can be classified as a phenomenon of disturbed liver wind, it is suggested that GE might be beneficial in treating HD. However, although current studies support GE for the prevention of diverse neurodegenerations such as HD, its detailed mechanisms remain elusive. Purpose: To investigate the molecular mechanism of GE in preventing HD by focusing on mitochondrial morphology, which is highly associated with HD etiology and thus proposed as a therapeutic target of neurodegenerations. Study design/methods: The overexpression of the mutant huntingtin (mHTT) gene in rat pheochromocytoma (PC12) cells was used as an in vitro cell model of HD. A filter retardation assay was applied to measure protein aggregations during HTT expression. Cotransfection with mitochondrial fusion and fission genes was used to test their relationships with HTT aggregates by monitoring with a confocal laser scanning microscope and filter retardation assay. Western blot analysis was used to estimate protein expression under different drug treatments or cotransfections with other related genes. Results: The overexpression of mutant but not normal HTT genes significantly resulted in protein aggregations in PC12 cells. GE dose-dependently attenuated mHTT-induced protein aggregations and free radical formations. GE significantly reversed mHTT-induced mitochondrial fragmentation and dysregulation of mitochondrial fusion and fission molecules. The overexpression of mitochondrial fusion genes attenuated mHTT-induced protein aggregations. Further, Mdivi-1, a DRP1 fission molecule inhibitor, significantly reversed mHTT-induced protein aggregations and mitochondrial fragmentation. Conclusion: GE attenuated mHTT aggregations through the control of mitochondrial fusion and the fission pathway.",
keywords = "Fission, Fusion, Gastrodia elata, Huntington's disease, Mitochondria",
author = "Huang, {Nai Kuei} and Lin, {Chung Chih} and Lin, {Yun Lian} and Huang, {Chuen Lin} and Chiou, {Chun Tang} and Lee, {Yi Chao} and Lee, {Shu Yi} and Huang, {Hung Tse} and Yang, {Ying Chen}",
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T1 - Morphological control of mitochondria as the novel mechanism of Gastrodia elata in attenuating mutant huntingtin-induced protein aggregations

AU - Huang, Nai Kuei

AU - Lin, Chung Chih

AU - Lin, Yun Lian

AU - Huang, Chuen Lin

AU - Chiou, Chun Tang

AU - Lee, Yi Chao

AU - Lee, Shu Yi

AU - Huang, Hung Tse

AU - Yang, Ying Chen

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Background: According to Compendium of Materia Medica, Gastrodia elata (GE) Blume as a top grade and frequently prescribed herbal medicine has been used in treating dizziness, headaches, and epilepsy, indicating a neuroprotective effect. Because GE is capable of suppressing a hyperactive liver and thus calming endogenous wind, and because Huntington's disease (HD) can be classified as a phenomenon of disturbed liver wind, it is suggested that GE might be beneficial in treating HD. However, although current studies support GE for the prevention of diverse neurodegenerations such as HD, its detailed mechanisms remain elusive. Purpose: To investigate the molecular mechanism of GE in preventing HD by focusing on mitochondrial morphology, which is highly associated with HD etiology and thus proposed as a therapeutic target of neurodegenerations. Study design/methods: The overexpression of the mutant huntingtin (mHTT) gene in rat pheochromocytoma (PC12) cells was used as an in vitro cell model of HD. A filter retardation assay was applied to measure protein aggregations during HTT expression. Cotransfection with mitochondrial fusion and fission genes was used to test their relationships with HTT aggregates by monitoring with a confocal laser scanning microscope and filter retardation assay. Western blot analysis was used to estimate protein expression under different drug treatments or cotransfections with other related genes. Results: The overexpression of mutant but not normal HTT genes significantly resulted in protein aggregations in PC12 cells. GE dose-dependently attenuated mHTT-induced protein aggregations and free radical formations. GE significantly reversed mHTT-induced mitochondrial fragmentation and dysregulation of mitochondrial fusion and fission molecules. The overexpression of mitochondrial fusion genes attenuated mHTT-induced protein aggregations. Further, Mdivi-1, a DRP1 fission molecule inhibitor, significantly reversed mHTT-induced protein aggregations and mitochondrial fragmentation. Conclusion: GE attenuated mHTT aggregations through the control of mitochondrial fusion and the fission pathway.

AB - Background: According to Compendium of Materia Medica, Gastrodia elata (GE) Blume as a top grade and frequently prescribed herbal medicine has been used in treating dizziness, headaches, and epilepsy, indicating a neuroprotective effect. Because GE is capable of suppressing a hyperactive liver and thus calming endogenous wind, and because Huntington's disease (HD) can be classified as a phenomenon of disturbed liver wind, it is suggested that GE might be beneficial in treating HD. However, although current studies support GE for the prevention of diverse neurodegenerations such as HD, its detailed mechanisms remain elusive. Purpose: To investigate the molecular mechanism of GE in preventing HD by focusing on mitochondrial morphology, which is highly associated with HD etiology and thus proposed as a therapeutic target of neurodegenerations. Study design/methods: The overexpression of the mutant huntingtin (mHTT) gene in rat pheochromocytoma (PC12) cells was used as an in vitro cell model of HD. A filter retardation assay was applied to measure protein aggregations during HTT expression. Cotransfection with mitochondrial fusion and fission genes was used to test their relationships with HTT aggregates by monitoring with a confocal laser scanning microscope and filter retardation assay. Western blot analysis was used to estimate protein expression under different drug treatments or cotransfections with other related genes. Results: The overexpression of mutant but not normal HTT genes significantly resulted in protein aggregations in PC12 cells. GE dose-dependently attenuated mHTT-induced protein aggregations and free radical formations. GE significantly reversed mHTT-induced mitochondrial fragmentation and dysregulation of mitochondrial fusion and fission molecules. The overexpression of mitochondrial fusion genes attenuated mHTT-induced protein aggregations. Further, Mdivi-1, a DRP1 fission molecule inhibitor, significantly reversed mHTT-induced protein aggregations and mitochondrial fragmentation. Conclusion: GE attenuated mHTT aggregations through the control of mitochondrial fusion and the fission pathway.

KW - Fission

KW - Fusion

KW - Gastrodia elata

KW - Huntington's disease

KW - Mitochondria

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