PubMed:23069675 JSONTXT 29 Projects

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Id Subject Object Predicate Lexical cue
T1 0-96 Sentence denotes Critical role of neuronal pentraxin 1 in mitochondria-mediated hypoxic-ischemic neuronal injury.
T2 97-246 Sentence denotes Developing brain is highly susceptible to hypoxic-ischemic (HI) injury leading to severe neurological disabilities in surviving infants and children.
T3 247-397 Sentence denotes Previously, we have reported induction of neuronal pentraxin 1 (NP1), a novel neuronal protein of long-pentraxin family, following HI neuronal injury.
T4 398-490 Sentence denotes Here, we investigated how this specific signal is propagated to cause the HI neuronal death.
T5 491-701 Sentence denotes We used wild-type (WT) and NP1 knockout (NP1-KO) mouse hippocampal cultures, modeled in vitro following exposure to oxygen glucose deprivation (OGD), and in vivo neonatal (P9-10) mouse model of HI brain injury.
T6 702-907 Sentence denotes Our results show induction of NP1 in primary hippocampal neurons following OGD exposure (4-8 h) and in the ipsilateral hippocampal CA1 and CA3 regions at 24-48 h post-HI compared to the contralateral side.
T7 908-1041 Sentence denotes We also found increased PTEN activity concurrent with OGD time-dependent (4-8 h) dephosphorylation of Akt (Ser473) and GSK-3β (Ser9).
T8 1042-1147 Sentence denotes OGD also caused a time-dependent decrease in the phosphorylation of Bad (Ser136), and Bax protein levels.
T9 1148-1421 Sentence denotes Immunofluorescence staining and subcellular fractionation analyses revealed increased mitochondrial translocation of Bad and Bax proteins from cytoplasm following OGD (4 h) and simultaneously increased release of Cyt C from mitochondria followed by activation of caspase-3.
T10 1422-1659 Sentence denotes NP1 protein was immunoprecipitated with Bad and Bax proteins; OGD caused increased interactions of NP1 with Bad and Bax, thereby, facilitating their mitochondrial translocation and dissipation of mitochondrial membrane potential (ΔΨ(m)).
T11 1660-1858 Sentence denotes This NP1 induction preceded the increased mitochondrial release of cytochrome C (Cyt C) into the cytosol, activation of caspase-3 and OGD time-dependent cell death in WT primary hippocampal neurons.
T12 1859-2116 Sentence denotes In contrast, in NP1-KO neurons there was no translocation of Bad and Bax from cytosol to the mitochondria, and no evidence of ΔΨ(m) loss, increased Cyt C release and caspase-3 activation following OGD; which resulted in significantly reduced neuronal death.
T13 2117-2240 Sentence denotes Our results indicate a regulatory role of NP1 in Bad/Bax-dependent mitochondrial release of Cyt C and caspase-3 activation.
T14 2241-2445 Sentence denotes Together our findings demonstrate a novel mechanism by which NP1 regulates mitochondria-driven hippocampal cell death; suggesting NP1 as a potential therapeutic target against HI brain injury in neonates.