title: Medicinal herbs Oenanthe javanica (Blume) DC., Casuarina equisetifolia L. and Sorghum bicolor (L.) Moench protect human cells from MPP+damage via inducing FBXO7 expression.
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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Collectively, our study provides new targets, FBXO7 and its regulator GATA2, for the development of potential treatments of PD.
authors.affiliation: Department of Neurology, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taipei 10507, Taiwan.
authors.forename: Chiung-Mei
authors.initials: CM
authors.lastname: Chen
authors.affiliation: Department of Neurology, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taipei 10507, Taiwan.
authors.forename: I-Cheng
authors.initials: IC
authors.lastname: Chen
authors.affiliation: Department of Life Science, National Taiwan Normal University, 88 Ting-Chou Road, Section 4, Taipei 11677, Taiwan.
authors.forename: Ying-Lin
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Department of Life Science, National Taiwan Normal University, 88 Ting-Chou Road, Section 4, Taipei 11677, Taiwan.
authors.forename: Te-Hsien
authors.initials: TH
authors.lastname: Lin
authors.affiliation: Department of Neurology, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taipei 10507, Taiwan.
authors.forename: Wan-Ling
authors.initials: WL
authors.lastname: Chen
authors.affiliation: Department of Neurology, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taipei 10507, Taiwan.
authors.forename: Chih-Ying
authors.initials: CY
authors.lastname: Chao
authors.affiliation: Department of Neurology, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taipei 10507, Taiwan.
authors.forename: Yih-Ru
authors.initials: YR
authors.lastname: Wu
authors.affiliation: Department of Life Science, National Taiwan Normal University, 88 Ting-Chou Road, Section 4, Taipei 11677, Taiwan.
authors.forename: Yeah-Ting
authors.initials: YT
authors.lastname: Lu
authors.affiliation: Center of Excellence for Drug Development, Industrial Technology Research Institute, Hsinchu 31040, Taiwan.
authors.forename: Cheng-Yu
authors.initials: CY
authors.lastname: Lee
authors.affiliation: Center of Excellence for Drug Development, Industrial Technology Research Institute, Hsinchu 31040, Taiwan.
authors.forename: Hong-Chi
authors.initials: HC
authors.lastname: Chien
authors.affiliation: Center of Excellence for Diagnostic Products, Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu 31040, Taiwan.
authors.forename: Ting-Shou
authors.initials: TS
authors.lastname: Chen
authors.affiliation: Department of Life Science, National Taiwan Normal University, 88 Ting-Chou Road, Section 4, Taipei 11677, Taiwan. Electronic address: t43019@ntnu.edu.tw.
authors.forename: Guey-Jen
authors.initials: GJ
authors.lastname: Lee-Chen
authors.affiliation: Department of Life Science, National Taiwan Normal University, 88 Ting-Chou Road, Section 4, Taipei 11677, Taiwan. Electronic address: t43003@ntnu.edu.tw.
authors.forename: Chi-Mei
authors.initials: CM
authors.lastname: Lee
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D050989:GATA2 Transcription Factor / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006540:Herbicides / Q000633:toxicity; D006801:Humans; D019684:Magnoliopsida; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009154:Mutation; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D031050:Oenanthe; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D045868:Sorghum; D047992:TNF Receptor-Associated Factor 2 / Q000378:metabolism
chemical_list: D044783:F-Box Proteins; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D006540:Herbicides; D018696:Neuroprotective Agents; D010936:Plant Extracts; D047992:TNF Receptor-Associated Factor 2; D046988:Proteasome Endopeptidase Complex; D015655:1-Methyl-4-phenylpyridinium
keywords: FBXO7; GATA2; Medicinal herbs; Promoter characterization; TRAF2