Oxidative status of DJ-1-dependent activation of dopamine synthesis through interaction of tyrosine hydroxylase and 4-dihydroxy-L-phenylalanine (L-DOPA) decarboxylase with DJ-1.
Parkinson disease (PD) is caused by loss of dopamine, which is synthesized from tyrosine by two enzymes, tyrosine hydroxylase (TH) and 4-dihydroxy-L-phenylalanine decarboxylase (DDC). DJ-1 is a causative gene for the familial form of PD, but little is known about the roles of DJ-1 in dopamine synthesis. In this study, we found that DJ-1 directly bound to TH and DDC and positively regulated their activities in human dopaminergic cells. Mutants of DJ-1 found in PD patients, including heterozygous mutants, lost their activity and worked as dominant-negative forms toward wild-type DJ-1. When cells were treated with H(2)O(2), 6-hydroxydopamine, or 1-methyl-4-phenylpyridinium, changes in activities of TH and DDC accompanied by oxidation of cysteine 106 of DJ-1 occurred. It was found that DJ-1 possessing Cys-106 with SH and SOH forms was active and that DJ-1 possessing Cys-106 with SO(2)H and SO(3)H forms was inactive in terms of stimulation of TH and DDC activities. These findings indicate an essential role of DJ-1 in dopamine synthesis and contribution of DJ-1 to the sporadic form of PD.
Ishikawa
Shizuma
S
Graduate School of Agriculture, Hokkaido University, Kita-ku, Sapporo 060-8589, Japan.
Taira
Takahiro
T
Niki
Takeshi
T
Takahashi-Niki
Kazuko
K
Maita
Chinatsu
C
Maita
Hiroshi
H
Ariga
Hiroyoshi
H
Iguchi-Ariga
Sanae M M
SM
D045744:Cell Line, Tumor; D004296:Dopa Decarboxylase / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019084:Fluorescent Antibody Technique, Indirect; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D009154:Mutation; D015513:Oncogene Proteins / Q000378:metabolism*; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D010300:Parkinson Disease / Q000201:enzymology; D000071617:Protein Deglycase DJ-1; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D014446:Tyrosine 3-Monooxygenase; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D004296:Dopa Decarboxylase; D010100:Oxygen
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