Journal article
Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage
Nature (London), Vol.404(6779), pp.787-790
04/13/2000
DOI: 10.1038/35008121
PMID: 10783895
Abstract
Diabetic hyperglycaemia causes a variety of pathological changes in small
vessels, arteries and peripheral nerves. Vascular endothelial
cells are an important target of hyperglycaemic damage, but the mechanisms
underlying this damage are not fully understood. Three seemingly independent
biochemical pathways are involved in the pathogenesis: glucose-induced activation
of protein kinase C isoforms; increased formation of glucose-derived
advanced glycation end-products; and increased glucose flux
through the aldose reductase pathway. The relevance of each
of these pathways is supported by animal studies in which pathway-specific
inhibitors prevent various hyperglycaemia-induced abnormalities.
Hyperglycaemia increases the production of reactive oxygen species inside
cultured bovine aortic endothelial cells. Here we show that
this increase in reactive oxygen species is prevented by an inhibitor of electron
transport chain complex II, by an uncoupler of oxidative phosphorylation,
by uncoupling protein-1 and by manganese superoxide dismutase. Normalizing
levels of mitochondrial reactive oxygen species with each of these agents
prevents glucose-induced activation of protein kinase C, formation of advanced
glycation end-products, sorbitol accumulation and NFκB activation.
Details
- Title: Subtitle
- Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage
- Creators
- Diane Edelstein - Albert Einstein College of Medicine, Diabetes Research CentreHans-Peter Hammes - Justus-Liebig University III Medical DepartmentPeter J OatesTakeshi Matsumura - Albert Einstein College of Medicine, Diabetes Research CentreDavid BeebeXue Liang Du - Albert Einstein College of Medicine, Diabetes Research CentreYasufumi Kaneda - Division of Gene Therapy Science, Osaka University Medical SchoolTakeshi Nishikawa - Albert Einstein College of Medicine, Diabetes Research Centre Kumamoto University School of Medicine, Department of MedicineSho-ichi Yamagishi - Albert Einstein College of Medicine, Diabetes Research CentreIda Giardino - Albert Einstein College of Medicine, Diabetes Research CentreMichael Brownlee - Albert Einstein College of Medicine, Diabetes Research CentreMark A Yorek - Department of Internal Medicine, University of Iowa
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.404(6779), pp.787-790
- DOI
- 10.1038/35008121
- PMID
- 10783895
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Language
- English
- Date published
- 04/13/2000
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984094652902771
Metrics
27 Record Views