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Transcriptional Regulation Of Tyrosinase By α-synuclein And Inhibitors

Posted on:2010-03-18Degree:DoctorType:Dissertation
Country:ChinaCandidate:J X ZhuangFull Text:PDF
GTID:1114360275990583Subject:Biochemistry and Molecular Biology
Abstract/Summary:PDF Full Text Request
Tyrosinase (1.14.18.1),widely distributed in nature,is a metalloenzyme oxidasewhich catalyzes two distinct reactions of melanin synthesis---the hydroxylation ofmonophenol and the oxidation of o-diphenol to the corresponding o-quinone.It is akey enzyme in melanin biosynthesis,involved in determining the color of mammalianskin and hair.Its abnormal expression is responsible for the various dermatologicaldisorders,such as melasama age spots,actinic damages.It also contributes toneuromelanin formation in the human brain and the neurodegeneration associatedwith Parkinson's disease.Tyrosinase inhibitors,therefore,should be clinically usefulfor the treatments of some dermatological disorders associated with melaninhyperpigmentation and also important in cosmetics for whitening and depigmentationafter sunburn.The inhibition of tyrosinase has been the subject of many studies.In the present paper,we Separate inibitors from natural plants and effects of themon the activity of mushroom tyrosniase have been studied.Then effects of them on themelanin content and regulation of melanogenesis have been studied.In the end,effects of inhibitors on dopamine content in fly were assay.In the process of ourscreening the tyrosinase inhibitors,we found that melanin content could be depressionby overexpressingα-synuclein in the cell.The result indicates that tyrosinase andParkinson's disease have correlation to some extent,so the regulation of tyrosinase inthe B 16F10 has been studied.The contents and results were as follows:Five compounds were seperated that can inhibit tyrosinase from CNSL:Cardoltrienes,Cardol diene,Cardnol trienes,Cardanol diene,Cardanol monone.Theinhibition mechanism of them against the activity of mushroom tyrosinase wasstudied.Effects of them on the melanin content and regulation of melanogenesis inthe B 16F 10 cell were also studied.Screening the tyrosinase inhibitors from drugs and studying their inhibitorymechanism have been conducted.Effects of inhibitors on dopamine content in fly were assay.Regulation ofmelanogenesis by overexpressingα-synuclein in the B 16F 10 was also studied.
Keywords/Search Tags:Tyrosinase, Inhibitors, Mechanism, α-synuclein, Regulation of melanogenesis
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