title: Overexpression of DJ-1/PARK7, the Parkinson's disease-related protein, improves mitochondrial function via Akt phosphorylation on threonine 308 in dopaminergic neuron-like cells.
abstract: DJ-1/PARK7, the Parkinson's disease-related protein, plays an important role in mitochondrial function. However, the mechanisms by which DJ-1 affects mitochondrial function are not fully understood. Akt is a promoter of neuron survival and is partly involved in the neurodegenerative process. This research aimed at investigating a possible relationship between DJ-1 and Akt signalling in regulating mitochondrial function in the dopaminergic neuron-like cells SH-SY5Y and PC-12. Overexpression of DJ-1 was firstly validated at both the transcriptional and translational levels after transit transfection with plasmid pcDNA3-Flag-DJ-1. Confocal fluorescence microscopy demonstrated that overexpression of DJ-1 increased the mitochondrial mass, but did not disrupt the mitochondrial morphology. In addition, mitochondrial complex I activity was raised in DJ-1-overexpressing cells, and this rise occurred with an increase in cellular adenosine 5'-triphosphate content. Moreover, immunoblotting demonstrated that the levels of phosphoinositide 3-kinase and the total Akt were not altered in DJ-1-overexpressing cells, and nor was the Akt phosphorylation on serine 473 changed. By contrast, Akt phosphorylation on threonine 308 was significantly augmented by overexpression of DJ-1, and the expression of glycogen synthase kinase-3beta, a downstream effector of Akt, was suppressed. In summary, these results suggest that overexpression of DJ-1 improves the mitochondrial function, at least in part, through a mechanism involving Akt phosphorylation on threonine 308.
authors.affiliation: Department of Anatomy, School of Preclinical Medicine, Beijing University of Chinese Medicine, 11 North 3rd Ring Eastern Road, Beijing, 100029, China.|Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Yi
authors.identifier: 0000-0002-7422-8206
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anatomy, School of Preclinical Medicine, Beijing University of Chinese Medicine, 11 North 3rd Ring Eastern Road, Beijing, 100029, China.
authors.forename: Xiao-Gang
authors.initials: XG
authors.lastname: Gong
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Zhen-Zhen
authors.initials: ZZ
authors.lastname: Wang
authors.affiliation: Department of Anatomy, School of Preclinical Medicine, Beijing University of Chinese Medicine, 11 North 3rd Ring Eastern Road, Beijing, 100029, China.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Sun
authors.affiliation: Department of Anatomy, School of Preclinical Medicine, Beijing University of Chinese Medicine, 11 North 3rd Ring Eastern Road, Beijing, 100029, China.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Guo
authors.affiliation: Center for Scientific Research, School of Preclinical Medicine, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Jing-Hong
authors.initials: JH
authors.lastname: Hu
authors.affiliation: Department of Anatomy, School of Preclinical Medicine, Beijing University of Chinese Medicine, 11 North 3rd Ring Eastern Road, Beijing, 100029, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Ma
authors.affiliation: Beijing Key Lab for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Science, China-Japan Friendship Hospital, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.|College of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, China.
authors.forename: Nai-Hong
authors.initials: NH
authors.lastname: Chen
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D059290:Dopaminergic Neurons / Q000378:metabolism*; D042967:Electron Transport Complex I / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism*; D010766:Phosphorylation; D000071617:Protein Deglycase DJ-1 / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D013912:Threonine / Q000378:metabolism
chemical_list: D013912:Threonine; D000255:Adenosine Triphosphate; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; C105131:PARK7 protein, human; C404267:PARK7 protein, rat; D000071617:Protein Deglycase DJ-1; D042967:Electron Transport Complex I
keywords: Akt; DJ-1; in vitro; mitochondrial function; phosphorylation