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Brain mitochondria from DJ-1 knockout mice show increased respiration-dependent hydrogen peroxide consumption.
Redox Biol. 2014; 2:667-72.RB

Abstract

Mutations in the DJ-1 gene have been shown to cause a rare autosomal-recessive genetic form of Parkinson's disease (PD). The function of DJ-1 and its role in PD development has been linked to multiple pathways, however its exact role in the development of PD has remained elusive. It is thought that DJ-1 may play a role in regulating reactive oxygen species (ROS) formation and overall oxidative stress in cells through directly scavenging ROS itself, or through the regulation of ROS scavenging systems such as glutathione (GSH) or thioredoxin (Trx) or ROS producing complexes such as complex I of the electron transport chain. Previous work in this laboratory has demonstrated that isolated brain mitochondria consume H2O2 predominantly by the Trx/Thioredoxin Reductase (TrxR)/Peroxiredoxin (Prx) system in a respiration dependent manner (Drechsel et al., Journal of Biological Chemistry, 2010). Therefore we wanted to determine if mitochondrial H2O2 consumption was altered in brains from DJ-1 deficient mice (DJ-1(-/-)). Surprisingly, DJ-1(-/-) mice showed an increase in mitochondrial respiration-dependent H2O2 consumption compared to controls. To determine the basis of the increased H2O2 consumption in DJ1(-/-) mice, the activities of Trx, Thioredoxin Reductase (TrxR), GSH, glutathione disulfide (GSSG) and glutathione reductase (GR) were measured. Compared to control mice, brains from DJ-1(-/-) mice showed an increase in (1) mitochondrial Trx activity, (2) GSH and GSSG levels and (3) mitochondrial glutaredoxin (GRX) activity. Brains from DJ-1(-/-) mice showed a decrease in mitochondrial GR activity compared to controls. The increase in the enzymatic activities of mitochondrial Trx and total GSH levels may account for the increased H2O2 consumption observed in the brain mitochondria in DJ-1(-/-) mice perhaps as an adaptive response to chronic DJ-1 deficiency.

Authors+Show Affiliations

Neuroscience Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, United States of America.Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, 12850 E. Montview Blvd, Aurora, CO 80045, United States of America.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24936441

Citation

Lopert, Pamela, and Manisha Patel. "Brain Mitochondria From DJ-1 Knockout Mice Show Increased Respiration-dependent Hydrogen Peroxide Consumption." Redox Biology, vol. 2, 2014, pp. 667-72.
Lopert P, Patel M. Brain mitochondria from DJ-1 knockout mice show increased respiration-dependent hydrogen peroxide consumption. Redox Biol. 2014;2:667-72.
Lopert, P., & Patel, M. (2014). Brain mitochondria from DJ-1 knockout mice show increased respiration-dependent hydrogen peroxide consumption. Redox Biology, 2, 667-72. https://doi.org/10.1016/j.redox.2014.04.010
Lopert P, Patel M. Brain Mitochondria From DJ-1 Knockout Mice Show Increased Respiration-dependent Hydrogen Peroxide Consumption. Redox Biol. 2014;2:667-72. PubMed PMID: 24936441.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Brain mitochondria from DJ-1 knockout mice show increased respiration-dependent hydrogen peroxide consumption. AU - Lopert,Pamela, AU - Patel,Manisha, Y1 - 2014/04/24/ PY - 2014/04/11/received PY - 2014/04/18/revised PY - 2014/04/22/accepted PY - 2014/6/18/entrez PY - 2014/6/18/pubmed PY - 2015/1/30/medline KW - 4-HNE, 4-hydroxyl-2-nonenal KW - 6OHDA, 6-hydroxydopamine KW - ASK1, apoptosis signal-regulating kinase 1 KW - BSA, Bovin Serum Albumin KW - Cox IV, complex IV KW - DA, dopaminergic KW - DJ-1 KW - DJ1-/-, DJ-1 knockout KW - GR, glutathione reductase KW - GRX, glutaredoxin KW - GSH, reduced glutathione KW - GSSG, oxidized glutathione KW - Gpx, glutathione peroxidase KW - H2O2, hydrogen peroxide KW - HEDS, 2-hydroxyethyl disulfide KW - MEF, mouse embryonic fibroblasts KW - MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - Mitochondria KW - Nrf2, nuclear factor erythroid 2-related factor KW - Oxidative stress KW - PD, Parkinson’s disease KW - PQ, paraquat KW - Parkinson’s disease KW - Prx, peroxiredoxin KW - ROS, reactive oxygen species KW - SNpc, substantia nigra pars compacta KW - TH, tyrosine hydroxylase KW - Thioredoxin KW - Thioredoxin reductase KW - Trx, thioredoxin KW - Trx1, cytosolic trx KW - Trx2, mitochondrial trx KW - TrxR, thioredoxin reductase KW - TrxR1, cytosolic TrxR KW - TrxR2, mitochondrial Trx SP - 667 EP - 72 JF - Redox biology JO - Redox Biol VL - 2 N2 - Mutations in the DJ-1 gene have been shown to cause a rare autosomal-recessive genetic form of Parkinson's disease (PD). The function of DJ-1 and its role in PD development has been linked to multiple pathways, however its exact role in the development of PD has remained elusive. It is thought that DJ-1 may play a role in regulating reactive oxygen species (ROS) formation and overall oxidative stress in cells through directly scavenging ROS itself, or through the regulation of ROS scavenging systems such as glutathione (GSH) or thioredoxin (Trx) or ROS producing complexes such as complex I of the electron transport chain. Previous work in this laboratory has demonstrated that isolated brain mitochondria consume H2O2 predominantly by the Trx/Thioredoxin Reductase (TrxR)/Peroxiredoxin (Prx) system in a respiration dependent manner (Drechsel et al., Journal of Biological Chemistry, 2010). Therefore we wanted to determine if mitochondrial H2O2 consumption was altered in brains from DJ-1 deficient mice (DJ-1(-/-)). Surprisingly, DJ-1(-/-) mice showed an increase in mitochondrial respiration-dependent H2O2 consumption compared to controls. To determine the basis of the increased H2O2 consumption in DJ1(-/-) mice, the activities of Trx, Thioredoxin Reductase (TrxR), GSH, glutathione disulfide (GSSG) and glutathione reductase (GR) were measured. Compared to control mice, brains from DJ-1(-/-) mice showed an increase in (1) mitochondrial Trx activity, (2) GSH and GSSG levels and (3) mitochondrial glutaredoxin (GRX) activity. Brains from DJ-1(-/-) mice showed a decrease in mitochondrial GR activity compared to controls. The increase in the enzymatic activities of mitochondrial Trx and total GSH levels may account for the increased H2O2 consumption observed in the brain mitochondria in DJ-1(-/-) mice perhaps as an adaptive response to chronic DJ-1 deficiency. SN - 2213-2317 UR - https://www.unboundmedicine.com/medline/citation/24936441/Brain_mitochondria_from_DJ_1_knockout_mice_show_increased_respiration_dependent_hydrogen_peroxide_consumption_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2213-2317(14)00063-9 DB - PRIME DP - Unbound Medicine ER -