Inhibition of tyrosine hydroxylase expression in alpha-synuclein-transfected dopaminergic neuronal cells.
Although the aberrant expression of alpha-synuclein (alpha-Syn) is toxic to dopaminergic neurons, little is known about the correlation between the abnormality of alpha-Syn and the expression of tyrosine hydroxylase (TH), a rate-limiting enzyme for the synthesis of dopamine neurotransmitter. In this study, the MES23.5 rat dopaminergic cell line transfected with wild-type human alpha-Syn cDNA (h alpha-Syn) construct was used to investigate the association between alpha-Syn and TH. Immunocytochemical staining and Western blot for TH showed that the TH expression was greatly decreased in h alpha-Syn-transfected cells. Northern blot confirmed that the TH mRNA level was also dramatically reduced. Reduction of TH protein levels did not affect the growth and proliferation of the transfected cells. No apparent cell injury or death was observed. These results suggest that an abnormal expression of alpha-Syn may inhibit TH synthesis in dopaminergic cells.
Department of Neurobiology and the Sino-Japan Joint Laboratory on Neurodegenerative Diseases, Beijing Institute of Geriatrics, Xuanwu Hospital of the Capital University of Medical Sciences, 45 Changchun Street, Beijing 100053, China.
Shun
S
Yu
Xiaohong
X
Zuo
Yaohua
Y
Li
Chen
C
Zhang
Ming
M
Zhou
Yu Alex
YA
Zhang
Kenji
K
Uéda
Piu
P
Chan
D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D005455:Fluorescent Antibody Technique / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D051843:Synucleins; D014162:Transfection / Q000379:methods; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C497606:Snca protein, rat; D051843:Synucleins; D051844:alpha-Synuclein; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine