Medicinal herbs Oenanthe javanica (Blume) DC., Casuarina equisetifolia L. and Sorghum bicolor (L.) Moench protect human cells from MPP+ damage via inducing FBXO7 expression

Chiung Mei Chen, I. Cheng Chen, Ying Lin Chen, Te Hsien Lin, Wan Ling Chen, Chih Ying Chao, Yih Ru Wu, Yeah Ting Lu, Cheng Yu Lee, Hong Chi Chien, Ting Shou Chen, Guey-Jen Lee, Chi Mei Lee

Research output: Contribution to journalArticle

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Abstract

Background The F-box protein 7 (FBXO7) mutations have been identified in families with early-onset parkinsonism and pyramidal tract signs, and designated as PARK15. In addition, FBXO7 mutations were found in typical and young onset Parkinson's disease (PD). Evidence has also shown that FBXO7 plays an important role in the development of dopaminergic neurons and increased stability and overexpression of FBXO7 may be beneficial to PD. Purpose We screened extracts of medicinal herbs to enhance FBXO7 expression for neuroprotection in MPP+-treated cells. Methods Promoter reporter assay in HEK-293 cells was used to examine the cis/trans elements controlling FBXO7 expression and to screen extracts of medicinal herbs enhancing FBXO7 expression. MTT assay was performed to assess cell viability of MPP+-treated HEK-293/SH-SY5Y cells. In addition, proteasome activity, mitochondrial membrane potential and FBXO7/TRAF2/GATA2 protein expression were evaluated. Results We demonstrated that −202–−57 region of the FBXO7 promoter is likely to contain sequences that are bound by positive trans protein factors to activate FBXO7 expression and GATA2 is the main trans protein factor enhancing FBXO7 expression. Extracts of medicinal herbs Oenanthe javanica (Blume) DC. (Umbelliferae), Casuarina equisetifolia L. (Casuarinaceae), and Sorghum bicolor (L.) Moench (Gramineae) improved cell viability of both MPP+-treated HEK-293 and SH-SY5Y cells, rescued proteasome activity in MPP+-treated HEK-293 cells, and restored mitochondrial membrane potential in MPP+-treated SH-SY5Y cells. These protection effects of herbal extracts are acting through enhancing FBXO7 and decreasing TRAF2 expression, which is probably mediated by GATA2 induction. Conclusion Collectively, our study provides new targets, FBXO7 and its regulator GATA2, for the development of potential treatments of PD.

Original languageEnglish
Pages (from-to)1422-1433
Number of pages12
JournalPhytomedicine
Volume23
Issue number12
DOIs
Publication statusPublished - 2016 Nov 15

Fingerprint

Oenanthe
F-Box Proteins
Sorghum
Medicinal Plants
TNF Receptor-Associated Factor 2
Parkinson Disease
Mitochondrial Membrane Potential
HEK293 Cells
Proteasome Endopeptidase Complex
Cell Survival
Apiaceae
Pyramidal Tracts
Mutation
Proteins
Dopaminergic Neurons

Keywords

  • FBXO7
  • GATA2
  • Medicinal herbs
  • Promoter characterization
  • TRAF2

ASJC Scopus subject areas

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

Cite this

Medicinal herbs Oenanthe javanica (Blume) DC., Casuarina equisetifolia L. and Sorghum bicolor (L.) Moench protect human cells from MPP+ damage via inducing FBXO7 expression. / Chen, Chiung Mei; Chen, I. Cheng; Chen, Ying Lin; Lin, Te Hsien; Chen, Wan Ling; Chao, Chih Ying; Wu, Yih Ru; Lu, Yeah Ting; Lee, Cheng Yu; Chien, Hong Chi; Chen, Ting Shou; Lee, Guey-Jen; Lee, Chi Mei.

In: Phytomedicine, Vol. 23, No. 12, 15.11.2016, p. 1422-1433.

Research output: Contribution to journalArticle

Chen, Chiung Mei ; Chen, I. Cheng ; Chen, Ying Lin ; Lin, Te Hsien ; Chen, Wan Ling ; Chao, Chih Ying ; Wu, Yih Ru ; Lu, Yeah Ting ; Lee, Cheng Yu ; Chien, Hong Chi ; Chen, Ting Shou ; Lee, Guey-Jen ; Lee, Chi Mei. / Medicinal herbs Oenanthe javanica (Blume) DC., Casuarina equisetifolia L. and Sorghum bicolor (L.) Moench protect human cells from MPP+ damage via inducing FBXO7 expression. In: Phytomedicine. 2016 ; Vol. 23, No. 12. pp. 1422-1433.
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abstract = "Background The F-box protein 7 (FBXO7) mutations have been identified in families with early-onset parkinsonism and pyramidal tract signs, and designated as PARK15. In addition, FBXO7 mutations were found in typical and young onset Parkinson's disease (PD). Evidence has also shown that FBXO7 plays an important role in the development of dopaminergic neurons and increased stability and overexpression of FBXO7 may be beneficial to PD. Purpose We screened extracts of medicinal herbs to enhance FBXO7 expression for neuroprotection in MPP+-treated cells. Methods Promoter reporter assay in HEK-293 cells was used to examine the cis/trans elements controlling FBXO7 expression and to screen extracts of medicinal herbs enhancing FBXO7 expression. MTT assay was performed to assess cell viability of MPP+-treated HEK-293/SH-SY5Y cells. In addition, proteasome activity, mitochondrial membrane potential and FBXO7/TRAF2/GATA2 protein expression were evaluated. Results We demonstrated that −202–−57 region of the FBXO7 promoter is likely to contain sequences that are bound by positive trans protein factors to activate FBXO7 expression and GATA2 is the main trans protein factor enhancing FBXO7 expression. Extracts of medicinal herbs Oenanthe javanica (Blume) DC. (Umbelliferae), Casuarina equisetifolia L. (Casuarinaceae), and Sorghum bicolor (L.) Moench (Gramineae) improved cell viability of both MPP+-treated HEK-293 and SH-SY5Y cells, rescued proteasome activity in MPP+-treated HEK-293 cells, and restored mitochondrial membrane potential in MPP+-treated SH-SY5Y cells. These protection effects of herbal extracts are acting through enhancing FBXO7 and decreasing TRAF2 expression, which is probably mediated by GATA2 induction. Conclusion Collectively, our study provides new targets, FBXO7 and its regulator GATA2, for the development of potential treatments of PD.",
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AU - Chen, Chiung Mei

AU - Chen, I. Cheng

AU - Chen, Ying Lin

AU - Lin, Te Hsien

AU - Chen, Wan Ling

AU - Chao, Chih Ying

AU - Wu, Yih Ru

AU - Lu, Yeah Ting

AU - Lee, Cheng Yu

AU - Chien, Hong Chi

AU - Chen, Ting Shou

AU - Lee, Guey-Jen

AU - Lee, Chi Mei

PY - 2016/11/15

Y1 - 2016/11/15

N2 - Background The F-box protein 7 (FBXO7) mutations have been identified in families with early-onset parkinsonism and pyramidal tract signs, and designated as PARK15. In addition, FBXO7 mutations were found in typical and young onset Parkinson's disease (PD). Evidence has also shown that FBXO7 plays an important role in the development of dopaminergic neurons and increased stability and overexpression of FBXO7 may be beneficial to PD. Purpose We screened extracts of medicinal herbs to enhance FBXO7 expression for neuroprotection in MPP+-treated cells. Methods Promoter reporter assay in HEK-293 cells was used to examine the cis/trans elements controlling FBXO7 expression and to screen extracts of medicinal herbs enhancing FBXO7 expression. MTT assay was performed to assess cell viability of MPP+-treated HEK-293/SH-SY5Y cells. In addition, proteasome activity, mitochondrial membrane potential and FBXO7/TRAF2/GATA2 protein expression were evaluated. Results We demonstrated that −202–−57 region of the FBXO7 promoter is likely to contain sequences that are bound by positive trans protein factors to activate FBXO7 expression and GATA2 is the main trans protein factor enhancing FBXO7 expression. Extracts of medicinal herbs Oenanthe javanica (Blume) DC. (Umbelliferae), Casuarina equisetifolia L. (Casuarinaceae), and Sorghum bicolor (L.) Moench (Gramineae) improved cell viability of both MPP+-treated HEK-293 and SH-SY5Y cells, rescued proteasome activity in MPP+-treated HEK-293 cells, and restored mitochondrial membrane potential in MPP+-treated SH-SY5Y cells. These protection effects of herbal extracts are acting through enhancing FBXO7 and decreasing TRAF2 expression, which is probably mediated by GATA2 induction. Conclusion Collectively, our study provides new targets, FBXO7 and its regulator GATA2, for the development of potential treatments of PD.

AB - Background The F-box protein 7 (FBXO7) mutations have been identified in families with early-onset parkinsonism and pyramidal tract signs, and designated as PARK15. In addition, FBXO7 mutations were found in typical and young onset Parkinson's disease (PD). Evidence has also shown that FBXO7 plays an important role in the development of dopaminergic neurons and increased stability and overexpression of FBXO7 may be beneficial to PD. Purpose We screened extracts of medicinal herbs to enhance FBXO7 expression for neuroprotection in MPP+-treated cells. Methods Promoter reporter assay in HEK-293 cells was used to examine the cis/trans elements controlling FBXO7 expression and to screen extracts of medicinal herbs enhancing FBXO7 expression. MTT assay was performed to assess cell viability of MPP+-treated HEK-293/SH-SY5Y cells. In addition, proteasome activity, mitochondrial membrane potential and FBXO7/TRAF2/GATA2 protein expression were evaluated. Results We demonstrated that −202–−57 region of the FBXO7 promoter is likely to contain sequences that are bound by positive trans protein factors to activate FBXO7 expression and GATA2 is the main trans protein factor enhancing FBXO7 expression. Extracts of medicinal herbs Oenanthe javanica (Blume) DC. (Umbelliferae), Casuarina equisetifolia L. (Casuarinaceae), and Sorghum bicolor (L.) Moench (Gramineae) improved cell viability of both MPP+-treated HEK-293 and SH-SY5Y cells, rescued proteasome activity in MPP+-treated HEK-293 cells, and restored mitochondrial membrane potential in MPP+-treated SH-SY5Y cells. These protection effects of herbal extracts are acting through enhancing FBXO7 and decreasing TRAF2 expression, which is probably mediated by GATA2 induction. Conclusion Collectively, our study provides new targets, FBXO7 and its regulator GATA2, for the development of potential treatments of PD.

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KW - GATA2

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KW - Promoter characterization

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