Gastrodia elata prevents huntingtin aggregations through activation of the adenosine A 2A receptor and ubiquitin proteasome system

Chuen Lin Huang, Jung Mou Yang, Kaw Chen Wang, Yi Chao Lee, Yun Lian Lin, Ying Chen Yang, Nai Kuei Huang

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Ethnopharmacological relevance: Gastrodia elata Blume (Fam. Orchidaceae) is a traditional Chinese herbal medicine for treating headaches, dizziness, tetanus, epilepsy, and numbness of the limbs, which suggests that it has neuroprotective effect. Aim of the study: To validate the neuroprotection of Gastrodia elata in preventing neurodegenerations, such as Huntington's disease (HD). Materials and methods: MTT assay was used to validate the protection of Gastrodia elata. In pheochromocytoma (PC12) cell. Transient transfection of mutant huntingtin (Htt) in PC12 cell was used as an in vitro model of HD. Filter retardation assay was used to measure Htt-induced protein aggregations. Proteasome activity was monitored by transfection of pZsProSensor-1 and imaged by a confocal laser scanning microscope. Results: This protection of Gastrodia elata could be blocked by an A 2A-R antagonist and a protein kinase A (PKA) inhibitor, indicating an A 2A-R signaling event. Gastrodia elata could reverse mutant Htt-induced protein aggregations and proteasome de-activation through A 2A-R signaling. In addition, activation of PKA tended to activate proteasome activity and reduce mutant Htt protein aggregations. The proteasome inhibitor, MG 132, blocked Gastrodia elata-mediated suppression of mutant Htt aggregations. Conclusion: Gastrodia elata prevented mutant Htt aggregations and increased proteasomal activity by targeting the A 2A-R through PKA-dependent pathway.

Original languageEnglish
Pages (from-to)162-168
Number of pages7
JournalJournal of Ethnopharmacology
Volume138
Issue number1
DOIs
Publication statusPublished - Oct 31 2011
Externally publishedYes

Fingerprint

Gastrodia
Adenosine A2A Receptors
Proteasome Endopeptidase Complex
Ubiquitin
Cyclic AMP-Dependent Protein Kinases
PC12 Cells
Huntington Disease
Mutant Proteins
Transfection
Orchidaceae
Proteasome Inhibitors
Hypesthesia
Herbal Medicine
Tetanus
Dizziness
Pheochromocytoma
Neuroprotective Agents
Protein Kinase Inhibitors
Headache
Epilepsy

Keywords

  • Gastrodia elata
  • Huntington's disease
  • Polyglutamine
  • Ubiquitin proteasome system

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

Gastrodia elata prevents huntingtin aggregations through activation of the adenosine A 2A receptor and ubiquitin proteasome system. / Huang, Chuen Lin; Yang, Jung Mou; Wang, Kaw Chen; Lee, Yi Chao; Lin, Yun Lian; Yang, Ying Chen; Huang, Nai Kuei.

In: Journal of Ethnopharmacology, Vol. 138, No. 1, 31.10.2011, p. 162-168.

Research output: Contribution to journalArticle

Huang, Chuen Lin ; Yang, Jung Mou ; Wang, Kaw Chen ; Lee, Yi Chao ; Lin, Yun Lian ; Yang, Ying Chen ; Huang, Nai Kuei. / Gastrodia elata prevents huntingtin aggregations through activation of the adenosine A 2A receptor and ubiquitin proteasome system. In: Journal of Ethnopharmacology. 2011 ; Vol. 138, No. 1. pp. 162-168.
@article{a0ba7250d1234914ad9400d1673bd770,
title = "Gastrodia elata prevents huntingtin aggregations through activation of the adenosine A 2A receptor and ubiquitin proteasome system",
abstract = "Ethnopharmacological relevance: Gastrodia elata Blume (Fam. Orchidaceae) is a traditional Chinese herbal medicine for treating headaches, dizziness, tetanus, epilepsy, and numbness of the limbs, which suggests that it has neuroprotective effect. Aim of the study: To validate the neuroprotection of Gastrodia elata in preventing neurodegenerations, such as Huntington's disease (HD). Materials and methods: MTT assay was used to validate the protection of Gastrodia elata. In pheochromocytoma (PC12) cell. Transient transfection of mutant huntingtin (Htt) in PC12 cell was used as an in vitro model of HD. Filter retardation assay was used to measure Htt-induced protein aggregations. Proteasome activity was monitored by transfection of pZsProSensor-1 and imaged by a confocal laser scanning microscope. Results: This protection of Gastrodia elata could be blocked by an A 2A-R antagonist and a protein kinase A (PKA) inhibitor, indicating an A 2A-R signaling event. Gastrodia elata could reverse mutant Htt-induced protein aggregations and proteasome de-activation through A 2A-R signaling. In addition, activation of PKA tended to activate proteasome activity and reduce mutant Htt protein aggregations. The proteasome inhibitor, MG 132, blocked Gastrodia elata-mediated suppression of mutant Htt aggregations. Conclusion: Gastrodia elata prevented mutant Htt aggregations and increased proteasomal activity by targeting the A 2A-R through PKA-dependent pathway.",
keywords = "Gastrodia elata, Huntington's disease, Polyglutamine, Ubiquitin proteasome system",
author = "Huang, {Chuen Lin} and Yang, {Jung Mou} and Wang, {Kaw Chen} and Lee, {Yi Chao} and Lin, {Yun Lian} and Yang, {Ying Chen} and Huang, {Nai Kuei}",
year = "2011",
month = "10",
day = "31",
doi = "10.1016/j.jep.2011.08.075",
language = "English",
volume = "138",
pages = "162--168",
journal = "Journal of Ethnopharmacology",
issn = "0378-8741",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

TY - JOUR

T1 - Gastrodia elata prevents huntingtin aggregations through activation of the adenosine A 2A receptor and ubiquitin proteasome system

AU - Huang, Chuen Lin

AU - Yang, Jung Mou

AU - Wang, Kaw Chen

AU - Lee, Yi Chao

AU - Lin, Yun Lian

AU - Yang, Ying Chen

AU - Huang, Nai Kuei

PY - 2011/10/31

Y1 - 2011/10/31

N2 - Ethnopharmacological relevance: Gastrodia elata Blume (Fam. Orchidaceae) is a traditional Chinese herbal medicine for treating headaches, dizziness, tetanus, epilepsy, and numbness of the limbs, which suggests that it has neuroprotective effect. Aim of the study: To validate the neuroprotection of Gastrodia elata in preventing neurodegenerations, such as Huntington's disease (HD). Materials and methods: MTT assay was used to validate the protection of Gastrodia elata. In pheochromocytoma (PC12) cell. Transient transfection of mutant huntingtin (Htt) in PC12 cell was used as an in vitro model of HD. Filter retardation assay was used to measure Htt-induced protein aggregations. Proteasome activity was monitored by transfection of pZsProSensor-1 and imaged by a confocal laser scanning microscope. Results: This protection of Gastrodia elata could be blocked by an A 2A-R antagonist and a protein kinase A (PKA) inhibitor, indicating an A 2A-R signaling event. Gastrodia elata could reverse mutant Htt-induced protein aggregations and proteasome de-activation through A 2A-R signaling. In addition, activation of PKA tended to activate proteasome activity and reduce mutant Htt protein aggregations. The proteasome inhibitor, MG 132, blocked Gastrodia elata-mediated suppression of mutant Htt aggregations. Conclusion: Gastrodia elata prevented mutant Htt aggregations and increased proteasomal activity by targeting the A 2A-R through PKA-dependent pathway.

AB - Ethnopharmacological relevance: Gastrodia elata Blume (Fam. Orchidaceae) is a traditional Chinese herbal medicine for treating headaches, dizziness, tetanus, epilepsy, and numbness of the limbs, which suggests that it has neuroprotective effect. Aim of the study: To validate the neuroprotection of Gastrodia elata in preventing neurodegenerations, such as Huntington's disease (HD). Materials and methods: MTT assay was used to validate the protection of Gastrodia elata. In pheochromocytoma (PC12) cell. Transient transfection of mutant huntingtin (Htt) in PC12 cell was used as an in vitro model of HD. Filter retardation assay was used to measure Htt-induced protein aggregations. Proteasome activity was monitored by transfection of pZsProSensor-1 and imaged by a confocal laser scanning microscope. Results: This protection of Gastrodia elata could be blocked by an A 2A-R antagonist and a protein kinase A (PKA) inhibitor, indicating an A 2A-R signaling event. Gastrodia elata could reverse mutant Htt-induced protein aggregations and proteasome de-activation through A 2A-R signaling. In addition, activation of PKA tended to activate proteasome activity and reduce mutant Htt protein aggregations. The proteasome inhibitor, MG 132, blocked Gastrodia elata-mediated suppression of mutant Htt aggregations. Conclusion: Gastrodia elata prevented mutant Htt aggregations and increased proteasomal activity by targeting the A 2A-R through PKA-dependent pathway.

KW - Gastrodia elata

KW - Huntington's disease

KW - Polyglutamine

KW - Ubiquitin proteasome system

UR - http://www.scopus.com/inward/record.url?scp=80255123778&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80255123778&partnerID=8YFLogxK

U2 - 10.1016/j.jep.2011.08.075

DO - 10.1016/j.jep.2011.08.075

M3 - Article

VL - 138

SP - 162

EP - 168

JO - Journal of Ethnopharmacology

JF - Journal of Ethnopharmacology

SN - 0378-8741

IS - 1

ER -