| Pyruvate ameliorates post ischemic injury of rat astrocytes and protects them against PARP mediated cell death. | |
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MedLine Citation:
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PMID: 14604778 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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This in vitro study was designed to examine the efficacy of exogenous pyruvate and glucose as a fuel substrate to protect rat astrocytes from post-ischemic injury. Astrocytes were incubated in Kreb's buffer deprived of oxygen and glucose for 6 h (ischemia) followed by incubation with added pyruvate or glucose and normoxia for the next 6 h (reperfusion). The transformation of reactive astrocytes in response to various treatments was examined by immunostaining with glial fibrillary acidic protein. The extent of cell damage was evaluated in terms of lactate dehydrogenase leakage from the cells and altered intracellular redox status. The mechanism of cell death was determined by immunoblotting with cytochrome C, caspase-3 and PARP antibodies. The mechanism of the action of pyruvate was determined by measuring the activity of pyruvate dehydrogenase complex, and cellular metabolic status by measuring ATP levels. In comparison to glucose, supply of exogenous pyruvate restored the morphological integrity of post-ischemic astrocytes and prevented gliosis. Pyruvate prevented the cell death of post-ischemic astrocytes by inhibiting the leakage of lactate dehydrogenase, decreasing the redox ratio and restraining the activation of apoptotic events such as release of mitochondrial cytochrome c and fragmentation of caspase-3 and PARP. This study also suggests that pyruvate may accelerate its own metabolism by increasing the activity of pyruvate dehydrogenase and thus restores the cellular ATP levels in post-ischemic astrocytes. Use of pyruvate as an alternate fuel substrate may provide a possibility for the novel therapeutic approach to the treatment of cerebral ischemia. |
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Authors:
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Pushpa Sharma; John Karian; Swapnil Sharma; Suzhen Liu; Paul D Mongan |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Brain research Volume: 992 ISSN: 0006-8993 ISO Abbreviation: Brain Res. Publication Date: 2003 Nov |
Date Detail:
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Created Date: 2003-11-07 Completed Date: 2004-01-22 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0045503 Medline TA: Brain Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 104-13 Citation Subset: IM |
Affiliation:
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Department of Anesthesiology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. psharma@usuhs.mil |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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analysis Animals Astrocytes / drug effects*, metabolism, pathology Cell Death Cells, Cultured Glial Fibrillary Acidic Protein / metabolism Glucose / pharmacology Immunohistochemistry Ischemia / metabolism* Neuroprotective Agents / pharmacology* Poly(ADP-ribose) Polymerases / pharmacology Pyruvate Dehydrogenase Complex / metabolism Pyruvic Acid / pharmacology* Rats Rats, Sprague-Dawley |
| Chemical | |
Reg. No./Substance:
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0/Glial Fibrillary Acidic Protein; 0/Neuroprotective Agents; 0/Pyruvate Dehydrogenase Complex; 127-17-3/Pyruvic Acid; 50-99-7/Glucose; 56-65-5/Adenosine Triphosphate; EC 2.4.2.30/Poly(ADP-ribose) Polymerases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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