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| Content Provider | Springer Nature Link |
|---|---|
| Author | Fiskum, Gary Rosenthal, Robert E. Vereczki, Viktoria Martin, Erica Hoffman, Gloria E. Chipoulos, Christos Kowaltowski, Alicia |
| Copyright Year | 2004 |
| Abstract | Mitochondria are both targets and sources of oxidative stress. This dual relationship is particularly evident in experimental paradigms modeling ischemic brain injury. One mitochondrial metabolic enzyme that is particularly sensitive to oxidative inactivation is pyruvate dehydrogenase. This reaction is extremely important in the adult CNS that relies very heavily on carbohydrate metabolism, as it represents the sole bridge between anaerobic and aerobic metabolism. Oxidative injury to this enzyme and to other metabolic enzymes proximal to the electron transport chain may be responsible for the oxidized shift in cellular redox state that is observed during approximately the first hour of cerebral reperfusion. In addition to impairing cerebral energy metabolism, oxidative stress is a potent activator of apoptosis. The mechanisms responsible for this activation are poorly understood but likely involve the expression of p53 and possibly direct effects of reactive oxygen species on mitochondrial membrane proteins and lipids. Mitochondria also normally generate reactive oxygen species and contribute significantly to the elevated net production of these destructive agents during reperfusion. Approaches to inhibiting pathologic mitochondrial generation of reactive oxygen species include mild uncoupling, pharmacologic inhibition of the membrane permeability transition, and simply lowering the concentration of inspired oxygen. Antideath mitochondrial proteins of the Bcl-2 family also confer cellular resistance to oxidative stress, paradoxically through stimulation of mitochondrial free radical generation and secondary upregulation of antioxidant gene expression. |
| Starting Page | 347 |
| Ending Page | 352 |
| Page Count | 6 |
| File Format | |
| ISSN | 0145479X |
| Journal | Journal of Bioenergetics and Biomembranes |
| Volume Number | 36 |
| Issue Number | 4 |
| e-ISSN | 15736881 |
| Language | English |
| Publisher | Kluwer Academic Publishers-Plenum Publishers |
| Publisher Date | 2004-01-01 |
| Publisher Place | New York |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Organic Chemistry Bioorganic Chemistry Biochemistry Animal Biochemistry Animal Anatomy / Morphology / Histology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Physiology |
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