The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
Resistance to cerebral ischemic injury in UCP2 knockout mice: evidence for a role of UCP2 as a regulator of mitochondrial glutathione levels
Open accessAbstract
Uncoupling protein 2 (UCP2) is suggested to be a regulator of reactive oxygen species production in mitochondria. We performed a detailed study of brain injury, including regional and cellular distribution of UCP2 mRNA, as well as measures of oxidative stress markers following permanent middle cerebral artery occlusion in UCP2 knockout (KO) and wild‐type (WT) mice. Three days post ischemia, there was a massive induction of UCP2 mRNA confined to microglia in the peri‐infarct area of WT mice. KO mice were less sensitive to ischemia as assessed by reduced brain infarct size, decreased densities of deoxyuridine triphosphate nick end‐labelling (TUNEL)‐labelled cells in the peri‐infact area and lower levels of lipid peroxidation compared with WT mice. This resistance may be related to the substantial increase of basal manganese superoxide dismutase levels in neurons of KO mice. Importantly, we found a specific decrease of mitochondrial glutathione (GSH) levels in UCP2 expressing microglia of WT, but not in KO mice after ischemia. This specific association between UCP2 and mitochondrial GSH levels regulation was further confirmed using lipopolysaccharide models of peripheral inflammation, and in purified peritoneal macrophages. Moreover, our data imply that UCP2 is not directly involved in the regulation of ROS production but acts by regulating mitochondrial GSH levels in microglia.
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“Consistent with these latter findings, knockout of UCP2 was found to be protective in a model of cerebral ischemic injury (110).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [110]
Citations
Cites
The Mouse Brain in Stereotaxic Coordinates
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Tietze, F. (1969) · Analytical Biochemistry · doi:10.1016/0003-2697(69)90064-5 · Cited by 6,077 · cited 4×
“Primary antibodies to Mn SOD (Calbiochem, San Diego, CA, USA, 1/200), cytochrome c antibody (Santa Cruz Biotechnology, Santa Cruz, CA, USA, 1/200) or cytochrome oxidase (COX) subunit IV (Molecular Probes, Eugene, OR, USA) were used.”
MethodInfluentialmouse brain in stereotaxic coordinates
Franklin, K. B. J., & Paxinos, G. (1997) · Cited by 3,258
Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia
Fleury, C., Neverova, M., Collins, S., Raimbault, S., Champigny, O., Lévi-Meyrueis, C., Bouillaud, F., Seldin, M. F., Surwit, R. S., Ricquier, D., et al. (1997) · Nature Genetics · doi:10.1038/ng0397-269 · Cited by 1,630 · cited 4×
“The UCP2 gene is expressed in most tissues (Fleury et al. 1997; Gimeno et al. 1997; Pecqueur et al. 2001) including brain (Richard et al.”
BackgroundInfluentialSelf-citationSuperoxide activates mitochondrial uncoupling proteins
Echtay, K. S., Roussel, D., St-Pierre, J., Jekabsons, M. B., Cadenas, S., Stuart, J. A., Harper, J. A., Roebuck, S. J., Morrison, A., Pickering, S., et al. (2002) · Nature · doi:10.1038/415096a · Cited by 1,382 · cited 2×
“In vitro studies also suggest thatUCP2may lead to an increase in proton conductance through interaction with superoxide (Echtay et al. 2002).”
BackgroundArsenijevic, D., Onuma, H., Pecqueur, C., Raimbault, S., Manning, B. S., Miroux, B., Couplan, E., Alves‐Guerra, M., Goubern, M., Surwit, R. S., et al. (2000) · Nature Genetics · doi:10.1038/82565 · Cited by 1,100 · cited 22×
“Consistent with the recent marked progress in this field, our data support the role of UCP2 in oxidative pathophys- iology (Arsenijevic et al. 2000; Blanc et al. 2003) and further contribute to the understanding of the physiological function of UCP2.”
BackgroundMethodResultInfluentialSelf-citationMitochondria, oxygen free radicals, disease and ageing
Raha, S., & Robinson, B. H. (2000) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)01674-1 · Cited by 1,066 · cited 1×
“It now appears that ROS production in mammalian cells is mainly a toxic by-product of the mitochondrial electron transport chain ( Raha and Robinson 2000 ).”
BackgroundRole of Oxidants in Ischemic Brain Damage
Chan, P. H. (1996) · Stroke · doi:10.1161/01.str.27.6.1124 · Cited by 1,027 · cited 1×
“ROS have been implicated in the pathogenesis of ischemic brain injury (Chan 1996).”
BackgroundZhang, C.-Y., Baffy, G., Perret, P., Krauss, S., Peroni, O., Grujic, D., Hagen, T., Vidal-Puig, A. J., Boss, O., Kim, Y.-B., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00378-6 · Cited by 917 · cited 2×
“Changes in mitochondrial levels of GSH have been described in pathological states associated with oxidative stress (particularly obesity, HIV, diabetes, cancer, inflammatory and infectious diseases ( Zaidan and Sims 1996; Szaleczky et al. 1999; Carretero et al. 2000; Perl and Banki 2000; Yang et al. 2000; Abou-Seif an…”
BackgroundUncoupling: new approaches to an old problem of bioenergetics
Skulachev, V. P. (1998) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(97)00091-1 · Cited by 893 · cited 2×
“Moreover, UCP2 has been implicated in the control of mitochondrial ROS levels (Negre-Salvayre et al. 1997; Lee et al. 1999; Arsenijevic et al. 2000; Yang et al. 2000; Li et al. 2001; Pecqueur et al. 2001) possibly by decreasing mitochondrial membrane potential (Skulachev 1998).”
Background
Research works printed but not linked: 1
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Cited by
Sorted by citations
The mitochondrial uncoupling-protein homologues
Krauss, S., Zhang, C., & Lowell, B. B. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1592 · Cited by 670
Redox regulation of mitochondrial function
Handy, D. E., & Loscalzo, J. (2012) · Antioxidants & Redox Signaling · doi:10.1089/ars.2011.4123 · Cited by 588
“Consistent with these latter findings, knockout of UCP2 was found to be protective in a model of cerebral ischemic injury (110).”
ResultMitochondrial uncoupling, ROS generation and cardioprotection
Cadenas, S. (2018) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2018.05.019 · Cited by 591
Ribas, V., García‐Ruiz, C., & Fernández-Checa, J. C. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00151 · Cited by 585
“Interestingly, a role for UCP2 in the transport of mGSH has been described in neurons, suggesting that the transport of protons back into the matrix by UCP2 may favor the movement of GSH (de Bilbao et al., 2004).”
BackgroundUncoupling proteins and the control of mitochondrial reactive oxygen species production
Mailloux, R. J., & Harper, M. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.06.022 · Cited by 547
“interconnected [133,134].”
Metadata
- Authors
- De Bilbao, F., Arsenijevic, D., Vallet, P., Hjelle, O. P., Ottersen, O. P., Bouras, C., Raffin, Y., Abou, K., Langhans, W., Collins, S., Plamondon, J., Alves‐Guerra, M., Haguenauer, A., Garcia, I., Richard, D., Ricquier, D., & Giannakopoulos, P.
- Affiliations
- ETH Zurich (CH)
- University Hospital of Geneva (CH)
- Duke University (US)
- Université Laval (CA)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Arsenijevic, Denis
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2004-04-26
- Volume
- 89
- Issue
- 5
- Pages
- 1283-1292
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2032327447
- Cited by
- 108
- References
- 61
- Citations by year
- 2026: 2 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 1 · 2019: 4 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 8 · 2014: 9 · 2013: 5 · 2012: 6
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Neurology › Neuroprotection in Cerebral Ischemia
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Keywords
- UCP2, cerebral ischemia, middle cerebral artery occlusion, microglia, mitochondrial glutathione, oxidative stress, manganese superoxide dismutase, lipid peroxidation, neuroprotection, UCP2 knockout mice, lipopolysaccharide-induced inflammation, peritoneal macrophages, reactive oxygen species
- MeSH terms
- Uncoupling Protein 2, Animals, Antioxidants, Cell Count, Brain Ischemia, Disease Models, Animal, Glutathione, Ion Channels, Lipopolysaccharides, Male, Mitochondria, RNA, Messenger, Superoxide Dismutase, Microglia, Macrophages, Peritoneal, Mice, Knockout, Oxidative Stress, Genetic Predisposition to Disease, In Situ Nick-End Labeling, Protein Transport, Mitochondrial Proteins, Membrane Transport Proteins, Cytochromes c, Mice
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