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. |