RGD Reference Report - Effects of scoparone on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells. - Rat Genome Database

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Effects of scoparone on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells.

Authors: Yang, YJ  Lee, HJ  Huang, HS  Lee, BK  Choi, HS  Lim, SC  Lee, CK  Lee, MK 
Citation: Yang YJ, etal., J Neurosci Res. 2009 Jun;87(8):1929-37.
RGD ID: 5128879
Pubmed: PMID:19185027   (View Abstract at PubMed)
DOI: DOI:10.1002/jnr.22009   (Journal Full-text)

The effects of scoparone on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells were investigated. PC12 cells treated with scoparone at concentrations of 100-200 microM showed a 128-136% increase in dopamine levels over the course of 24 hr. Scoparone significantly increased the secretion of dopamine into the culture medium. Under the same conditions, the activities of tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) were enhanced by treatment with 200 microM scoparone for 6-48 hr, but the activity of TH was regulated for a longer period than that of AADC. The intracellular levels of cyclic AMP and Ca(2+) were increased by treatment with 200 microM scoparone. The levels of TH mRNA and the phosphorylation of cyclic AMP-response element-binding protein (CREB) were also significantly increased by treatment with 200 microM scoparone. In addition, scoparone at a concentration of 200 microM stimulated the activities of cyclic AMP-dependent protein kinase (PKA), protein kinase C (PKC), and Ca(2+)/calmodulin kinase II (CaMK II). Finally, pretreatment with 200 microM scoparone reduced the cytotoxicity induced by L-DOPA (20-100 microM) at 24 hr. These results suggest that scoparone enhances dopamine biosynthesis by regulating TH activity and TH gene expression, which is mediated by the PKA, CREB, PKC, and CaMK II pathways, and protects cells from L-DOPA-induced cytotoxicity by inducing cyclic AMP-PKA systems in PC12 cells.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
DdcRatphytoalexin metabolic process  IEP scoparoneRGD 
ThRatphytoalexin metabolic process  IEP scoparoneRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ddc  (dopa decarboxylase)
Th  (tyrosine hydroxylase)


Additional Information