RGD Reference Report - Hypoxia-activated metabolic pathway stimulates phosphorylation of p300 and CBP in oxygen-sensitive cells. - Rat Genome Database

RGD Reference Report - Hypoxia-activated metabolic pathway stimulates phosphorylation of p300 and CBP in oxygen-sensitive cells. - Rat Genome Database

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General

Hypoxia-activated metabolic pathway stimulates phosphorylation of p300 and CBP in oxygen-sensitive cells.
Authors:	Zakrzewska, A Schnell, PO Striet, JB Hui, A Robbins, JR Petrovic, M Conforti, L Gozal, D Wathelet, MG Czyzyk-Krzeska, MF
Citation:	Zakrzewska A, etal., J Neurochem. 2005 Sep;94(5):1288-96. Epub 2005 Jul 5.
RGD ID:	2289914
Pubmed:	PMID:16000154 (View Abstract at PubMed)
PMCID:	PMC1411962 (View Article at PubMed Central)
DOI:	DOI:10.1111/j.1471-4159.2005.03293.x (Journal Full-text)
Transcription co-activators and histone acetyltransferases, p300 and cyclic AMP responsive element-binding protein-binding protein (CBP), participate in hypoxic activation of hypoxia-inducible genes. Here, we show that exposure of PC12 and cells to 1-10% oxygen results in hyperphosphorylation of p300/CBP. This response is fast, long lasting and specific for hypoxia, but not for hypoxia-mimicking agents such as desferioxamine or Co2+ ions. It is also cell-type specific and occurs in pheochromocytoma PC12 cells and the carotid body of rats but not in hepatoblastoma cells. The p300 hyperphosphorylation specifically depends on the release of intracellular calcium from inositol 1,4,5-triphosphate (IP3)-sensitive stores. However, it is not inhibited by pharmacological inhibitors of any of the kinases traditionally known to be directly or indirectly calcium regulated. On the other hand, p300 hyperphosphorylation is inhibited by several different inhibitors of the glucose metabolic pathway from generation of NADH by glyceraldehyde 3-phosphate dehydrogenase, through the transfer of NADH through the glycerol phosphate shuttle to ubiquinone and complex III of the mitochondrial respiratory chain. Inhibition of IP3-sensitive calcium stores decreases generation of ATP, and this inhibition is significantly stronger in hypoxia than in normoxia. We propose that the NADH glycerol phosphate shuttle participates in generating a pool of ATP that serves either as a co-factor or a modulator of the kinases involved in the phosphorylation of p300/CBP during hypoxia.

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Biological Process

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
response to calcium ion		IMP		2289914		RGD
response to hypoxia		IEP		2289914		RGD

Objects Annotated

Genes (Rattus norvegicus)

Ep300 (E1A binding protein p300)

Additional Information