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Pyruvate improves recovery after PARP-1-associated energy failure induced by oxidative stress in neonatal rat cerebrocortical slices.

Pyruvate improves recovery after PARP-1-associated energy failure induced by oxidative stress in neonatal rat cerebrocortical slices. Research Abstract Details 

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  • Pyruvate improves recovery after PARP-1-associated energy failure induced by oxidative stress in neonatal rat cerebrocortical slices. Abstract Text:

    jianying zengJianying Zeng,guo-yuan yangGuo-Yuan Yang,weihai yingWeihai Ying,mark kellyMark Kelly,kiyoshi hiraiKiyoshi Hirai,thomas l jamesThomas L James,raymond a swansonRaymond A Swanson,lawrence littLawrence Litt,

    Previous neuron and glial cell culture studies of excessive poly (ADP-ribose) polymerase (PARP-1) activation found NAD(+) depletion, glycolytic arrest, and cell death that could be avoided by exogenous tricarboxylic acid cycle (TCA) metabolites, especially pyruvate (pyr). Pyruvate neuroprotection has been attributed to cytosolic NAD(+) replenishment, TCA metabolism, and antioxidant activity. We investigated the first two mechanisms in respiring cerebrocortical slices after a 1-h H(2)O(2) exposure to activate PARP-1. H(2)O(2) was followed by a 4-h recovery with oxy-artificial cerebrospinal fluid superfusion having either: (1) no glucose (glc) or pyruvate; (2) 10 mmol/L glc only; (3) 10 mmol/L pyruvate only; (4) both 10 mmol/L glc and 10 mmol/L pyruvate. Poly-ADP-ribosylation was quantified from Western blots and immunohistochemistry. Perchloric acid extracts were quantified with 14.1 T (31)P nuclear magnetic resonance spectroscopy. Just after H(2)O(2) exposure, ATP and NAD(+) decreased by approximately 50%, PCr decreased by 75%, and the ADP/ATP ratio approximately doubled. ATP and NAD(+) changes, but not PCr changes, were nearly eliminated if PARP inhibitors accompanied the H(2)O(2). Recovery with both pyruvate and glc was better than with glc alone, having higher ATP (0.161 versus 0.075, P<0.01) and PCr levels (0.144 versus 0.078, P<0.01), and higher viable cell counts in TUNEL and Fluoro-Jade B staining. Two-dimensional [(1)H-(13)C] HSQC spectra showed metabolism during recovery of (13)C glc or pyr. Pyruvate metabolism was primarily via pyruvate dehydrogenase, with some via pyruvate carboxylation. Pyruvate superfusion of PARP-injured brain slices helps replenish NAD(+) while providing metabolic fuel. Although this augments recovery, a strong antioxidant role for pyruvate has not been ruled out.

    Pyruvate improves recovery after PARP-1-associated energy failure induced by oxidative stress in neonatal rat cerebrocortical slices. Publishing Authors By Initials

    j zengJ Zeng,gy yangGY Yang,w yingW Ying,m kellyM Kelly,k hiraiK Hirai,tl jamesTL James,ra swansonRA Swanson,l littL Litt,

    For similar animals: chordata: vertebrates: mammals: rodentia: muridae: murinae: rats: rats, sprague-dawley research abstracts see: animals: chordata: vertebrates: mammals: rodentia: muridae: murinae: rats: rats, sprague-dawley research

    PUBMED ID PMID:

    MEDLINE DATE:

    Pyruvate improves recovery after PARP-1-associated energy failure induced by oxidative stress in neonatal rat cerebrocortical slices. Journal Published:

    PUBLICATION TYPE: Research Support, N.I.H., Extr

    Journal: Journal of cerebral blood flow and metabolism : of

    VOLUME: 27

    Page Numbers: 304-15

    Journal Abbreviation: J. Cereb. Blood Flow Metab.

    ISSN: 0271-678X

    DAY: 24

    MONTH: 05

    YEAR: 2006

    Pyruvate improves recovery after PARP-1-associated energy failure induced by oxidative stress in neonatal rat cerebrocortical slices. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 8112566

    Pyruvate improves recovery after PARP-1-associated energy failure induced by oxidative stress in neonatal rat cerebrocortical slices. Keywords Mesh Terms:

    KEYWORDS: Rats, Sprague-Dawley

    MESH TERMS: pharmacology

    Chemical & Substance for Abstract: Pyruvate improves recovery after PARP-1-associated energy failure induced by oxidative stress in neonatal rat cerebrocortical slices. Information

    Substance Name: Poly(ADP-ribose) Polymerases

    Registry Number: EC 2.4.2.30

    Grant and Affiliation Information for Pyruvate improves recovery after PARP-1-associated energy failure induced by oxidative stress in neonatal rat cerebrocortical slices.

    AFFILIATION: Department of Anesthesia, University of California at San Francisco, 94143-0648, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NIGMS

    GRANT: R01 GM034767

    ACRONYM: GM

    MEDLINETA: J Cereb Blood Flow Metab

    REFSOURCE:

    DATABASENAME:

    ACCESSION NUMBER:

    Number Hits: 0

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