Pink1 Regulates Tyrosine Hydroxylase Expression and Dopamine Synthesis

Journal of Alzheimer's Disease : JAD
Lingling LuHui Yang

Abstract

PTEN induced putative kinase 1 (PINK1), also known as PARK6, is causally linked to familial Parkinsonism, and heterozygous loss of PINK1 is a risk factor for sporadic Parkinson's disease. However, little is known about its physiological function. Its deficiency was shown to decrease dopamine without significant loss of dopaminergic neurons. We investigated the mechanistic basis for this observation in the present study using dopaminergic MN9D cells. We found that PINK1 knockdown resulted in dopamine content to decrease with suppressed tyrosine hydroxylase expression in cells. Conversely, PINK1 overexpression increased tyrosine hydroxylase protein level. We also found that PINK1 deficiency blocked the nuclear translocation and activity of nuclear receptor-related 1, a transcription factor regulating tyrosine hydroxylase gene expression. These data suggest that PINK1 regulates tyrosine hydroxylase gene expression and dopamine content by modulating the transcriptional activity of nuclear receptor-related 1. Taken together, our results reveal a novel function of PINK1 in dopamine homeostasis.

References

Aug 5, 2000·Biochemical and Biophysical Research Communications·T IwawakiK Kobayashi
Aug 14, 2003·Experimental Cell Research·Elisabet HermansonThomas Perlmann
Apr 17, 2004·Science·Enza Maria ValenteNicholas W Wood
Sep 7, 2004·Annals of Neurology·Enza Maria ValenteAnna Rita Bentivoglio
Apr 13, 2005·Proceedings of the National Academy of Sciences of the United States of America·Alexandra BeilinaMark R Cookson
May 10, 2005·Brain Research. Brain Research Protocols·Lingling LuHui Yang
May 16, 2006·Movement Disorders : Official Journal of the Movement Disorder Society·Chiara CriscuoloGiuseppe De Michele
Jun 15, 2007·Proceedings of the National Academy of Sciences of the United States of America·Tohru KitadaJie Shen
Jun 27, 2007·Neuroscience Bulletin·Nan GaoBiao Chen
Jan 26, 2008·Proceedings of the National Academy of Sciences of the United States of America·M Emdadul HaqueDavid S Park
Oct 1, 2011·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Yoland SmithMahlon R DeLong
Oct 26, 2011·The International Journal of Biochemistry & Cell Biology·Lingling LuHui Yang
Jan 4, 2012·Journal of Molecular Neuroscience : MN·Ruth Mélida Sánchez-MoraGonzalo Arboleda
May 23, 2012·Molecules and Cells·Hyongjong Koh, Jongkyeong Chung
Nov 28, 2012·Nature Reviews. Neurology·Michel GoedertHeiko Braak
May 23, 2014·Current Topics in Behavioral Neurosciences·Susanne A Schneider, Jose A Obeso
Apr 20, 2016·The Journal of Cell Biology·Kenneth R PrydeAnthony H V Schapira
Oct 26, 2016·CNS Drugs·Maria Eliza FreitasSusan H Fox
Nov 4, 2016·Brain : a Journal of Neurology·Andreas PuschmannWolfdieter Springer
Jan 10, 2017·Frontiers in Neuroanatomy·Pamela Valdés, Bernard L Schneider
Apr 15, 2017·Neurochemistry International·Irene Lopez-FabuelJuan P Bolaños
Apr 25, 2017·Current Opinion in Cell Biology·Thomas G McWilliams, Miratul Mk Muqit

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Methods Mentioned

BETA
transfection
PCR
electrophoresis
fluorescence microscopy
immunoprecipitation
Co-immunoprecipitation
nuclear translocation

Software Mentioned

SPSS
Primer

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