Induction of parkin expression in the presence of oxidative stress.
Parkinson's disease (PD) is one of the most common neurodegenerative disorders. Gene mutations have been found in rare familial forms of PD, with mutations in parkin being the most common cause. Oxidative stresses have also been implicated as an important contributing factor in the pathogenesis of PD. Currently, there is accumulating evidence that parkin may play a role in maintaining mitochondrial function and preventing oxidative stress. We demonstrated here that parkin is up-regulated when SH-SY5Y dopaminergic neuroblastoma cells are exposed to the oxidant dopamine. The up-regulation of parkin appeared to be due to transcriptional activation as luciferase assays confirmed that specific parkin promoter constructs could confer enhanced transcriptional activation in response to dopamine. Moreover, this effect was also seen when SH-SY5Y cells were subjected to another oxidative stress, 1-methyl-4-phenylpyridinium. In parallel with these studies, we also observed similar transcriptional activation of the parkin coregulated gene by oxidative stress. This is the first demonstration that parkin expression is up-regulated by oxidative stresses and may suggest that this might be a general neuroprotective response of parkin to oxidative stresses.
Yang
Yan Xiang
YX
Medical Molecular Biology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK. y.yang@ich.ucl.ac.uk
Muqit
Miratul M K
MM
Latchman
David S
DS
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D045744:Cell Line, Tumor; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis; D009447:Neuroblastoma; D018384:Oxidative Stress / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014162:Transfection / Q000379:methods; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D008156:Luciferases; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine