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Effect of hypoxia on nuclear high affinity Ca 2+ ‐ATPase activity and nuclear Ca 2+ ‐influx in the cerebral cortex of newborn piglets (888.2)
Author(s) -
DelivoriaPapadopoulos Maria,
Wang Andy,
Malaeb Shadi,
Ashraf Qazi
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.888.2
Subject(s) - hypoxia (environmental) , medicine , endocrinology , phosphocreatine , atpase , chemistry , kinase , calcium , microbiology and biotechnology , biology , enzyme , biochemistry , oxygen , energy metabolism , organic chemistry
Nuclear calcium signals control a number of critical nuclear functions including regulation of transcription factors, cell cycle regulation, gene transcription and DNA replication. Previous studies have shown that during hypoxia, there is increase in intracellular Ca 2+‐ and in nuclear high affinity Ca 2+‐ ATPase activity in the cerebral cortex of newborn piglets.We test the hypothesis that hypoxia results in increased activity of high affinity Ca 2+‐ ATPase and increased concentration of Ca 2+ ‐influx in cortical neuronal nuclei of newborn piglets, and this hypoxia‐induced increase is Src kinase mediated.Piglets were divided into normoxic (Nx, n=4), hypoxic (Hx, n=4), and hypoxic pretreated with Src kinase inhibitor (Hx+Srci, n=4). Hypoxia was induced by decreasing FiO 2 to 0.07 for 1 hr. Src kinase inhibitor (PP2, 1.0 mg/kg i.v.) was administered 30 min prior to hypoxia. Hypoxia was documented by levels of ATP and phosphocreatine (PCr). Nuclear 45 Ca 2+ concentration and activity of high affinity Ca 2+ ‐ATPase was determined at 37°C for 30 min.Nuclear 45 Ca 2+ ‐influx (pmoles/mg protein) was 3.95±0.57 in Nx , 13.36±1.56 in Hx (p<0.05) and 9.61±2.76 in the Hx+Srci group. Ca 2+ ‐ATPase activity increased following hypoxia: from 244.66±73.55 nmol Pi/mg protein/h in the normoxic group to 426.33±94.99 nmol Pi/mg protein/h in the hypoxic group (p<0.05 vs. normoxic group). In the Hx+Srci group, the high affinity Ca 2+ ‐ATPase activity increased to 354.25±62.88 nmol Pi/mg protein/h (p<0.05 vs. hypoxic group). The data show that administration of PP2, a selective inhibitor of Src kinase, prevents the hypoxia‐induced increase in nuclear 45 Ca 2+ ‐influx concentration and Ca 2+ ‐ATPase activity.We conclude that the hypoxia‐induced increase in nuclear membrane high affinity Ca 2+ ‐ATPase activity is Src kinase‐mediated activation of the high affinity Ca 2+ ‐ATPase, a mechanism of ATP‐dependent Ca 2+ uptake may lead to increase in intranuclear Ca 2+ during hypoxia. Grant Funding Source : NIH HD200337