title: L10P mutation in DJ-1 gene induced oxidative stress and mitochondrial disfunction.
abstract: OBJECTIVE
  To investigate the effect of the L10P mutation on the cellular mitochondrial disfunction.
  
  
  METHODS
  Spectrophotometer, flow cytometry and electron microscope was utilized to examine cell viability, reactive oxygen species (ROS), mitochondrial transmembrane potential, complex I activity and mitochondrial morphous of the HEK293 monoclone cell lines, in which wild-type and L10P mutant DJ-1 protein are stably expressed.
  
  
  RESULTS
  Compared with the cell lines expressing empty vector, we found the ROS levels were elevated, the cell viability, mitochondrial transmembrane potential, complex I activity were reduced in the cells expressing L10P mutant DJ-1 protein (P<0.05). We also found mitochondria in these cells were swelling and some mitochondria were vacuolar degeneration. These phenomena were more obvious when rotenone was used. But in the cells expressing wild-type DJ-1, ROS levels were lower, the cell viability, mitochondrial transmembrane potential, and complex I activity were higher than other cell lines (P<0.05), especially under the induction of rotenone. These results suggested that L10P mutant DJ-1 protein probably lost the ability of anti-oxidative stress and affect the normal function of mitochondria.
  
  
  CONCLUSIONS
  The L10P DJ-1 mutation results in a toxic protein, which lacks the protective function of wild-type protein on mitochondria due to the decrease in the ability of anti-oxidative stress.
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008; State Key Laboratory of Medical Genetics, Changsha 410078; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha 410008; Neurodegenerative Disorders Research Center, Central South University, Changsha 410008, China.
authors.forename: Jifeng
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Dan
authors.initials: D
authors.lastname: He
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Jifeng
authors.initials: J
authors.lastname: Kang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha 410008; Neurodegenerative Disorders Research Center, Central South University, Changsha 410008, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha 410008; Neurodegenerative Disorders Research Center, Central South University, Changsha 410008, China.
authors.forename: Xinxiang
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008; State Key Laboratory of Medical Genetics, Changsha 410078; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha 410008; Neurodegenerative Disorders Research Center, Central South University, Changsha 410008, China.
authors.forename: Beisha
authors.initials: B
authors.lastname: Tang
mesh_terms: D002470:Cell Survival; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000473:pathology*; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics*; D018384:Oxidative Stress; D000071617:Protein Deglycase DJ-1; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D017382:Reactive Oxygen Species; D012402:Rotenone; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1