L10P mutation in DJ-1 gene induced oxidative stress and mitochondrial disfunction.
10.11817/j.issn.1672-7347.2015.12.001
- Author:
Jifeng GUO
1
,
2
,
3
,
4
;
Dan HE
5
;
Lei WANG
5
;
Jifeng KANG
5
;
Nan LI
1
,
3
,
4
;
Xinxiang YAN
1
,
3
,
4
;
Beisha TANG
1
,
2
,
3
,
4
Author Information
1. Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008
2. State Key Laboratory of Medical Genetics, Changsha 410078
3. Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha 410008
4. Neurodegenerative Disorders Research Center, Central South University, Changsha 410008, China.
5. Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.
- Publication Type:Journal Article
- MeSH:
Cell Survival;
HEK293 Cells;
Humans;
Intracellular Signaling Peptides and Proteins;
genetics;
Membrane Potential, Mitochondrial;
Mitochondria;
pathology;
Mutation;
Oncogene Proteins;
genetics;
Oxidative Stress;
Protein Deglycase DJ-1;
Reactive Oxygen Species;
metabolism;
Rotenone
- From:
Journal of Central South University(Medical Sciences)
2015;40(12):1285-1291
- CountryChina
- Language:English
-
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.
CONCLUSION: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.
