Tetrahydrobiopterin-dependent Production of L-DOPA in Genetically Modified Primary Fibroblasts: Basic Research of Gene Therapy for Parkinson's Disease

Although intracerebral transplantation might become a new strategy for the treatment of neurological diseases, there are many problems for the grafts, We examined the possibilities of primary skin fibroblasts as a new graft for Parkinson's disease. Rat primary skin fibroblasts were transfected...

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Veröffentlicht in:Pteridines 1996-11, Vol.7 (4), p.151-153
Hauptverfasser: Ishida, Akihiko, Yamashiro, Katsumi, Mukawa, Jiro, Hasegawa, Mamoru
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Sprache:eng
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Zusammenfassung:Although intracerebral transplantation might become a new strategy for the treatment of neurological diseases, there are many problems for the grafts, We examined the possibilities of primary skin fibroblasts as a new graft for Parkinson's disease. Rat primary skin fibroblasts were transfected with a retrovirus vector containing eDNA of human tyrosine hydroxylast typel (TH) (pLTHSNL) or cytomegalovirus promoter (pCTHSNL) as a foreign promoter. In these genetically modified fibroblasts, catecholamine production and release were analyzed in vitro by immunocytochemistry and high performance liquid chromatography with electrochemical detection (HPLC-ECD), Being supplemented with biopterin (BH ; (6R)-L-erythro-tetrahydrobiopterin) cofactors required for TH activity, these cells produced and released L-DOPA into the culture medium. When combined with a foreign promoter and BH , L-DOPA production increased in a timedependent manner, which was not affected by the number of cell-passages and the duration of liquid nitrogen freezing . These facts suggest that the amount of L-DOPA secreted from transplanted genetically modified fibroblasts can be manipulated by an inserted promoter the exogenously administered BH . Thus genetically modified primary skin fibroblasts transfected with THcDNA using retrovirus vector system may hold promise as a graft for transplantation and gene therapy for Parkinson's disease.
ISSN:0933-4807
2195-4720
DOI:10.1515/pteridines.1996.7.4.151