Erasure of kinase phosphorylation in astrocytes during oxygen-glucose deprivation is controlled by ATP levels and activation of phosphatases.

Abstract

We have examined the relationship between adenosine triphosphate (ATP) concentration and loss of maintenance of kinase-signalling cascades in primary cortical astrocytes during oxygen-glucose deprivation (OGD) as this may constitute an irreversible step that commits astrocytes to cell death. We report that the phosphorylation of Akt, ERK, JNK and p38 kinases, whose activities depend on serine, threonine and tyrosine phosphorylation, were all increased during OGD. All these phosphorylations were reduced to below detection limits when ATP levels were less than 10% of normal levels. Using ERK and Akt as representative examples, we show that this erasure is not irreversible as both ERK and Akt phosphorylations can be partially restored by addition of glucose under anoxic conditions. We further investigated whether OGD caused any change in phosphatase activity. The PP1/PP2A phosphatase inhibitors okadaic acid and caliculyn A, but not cyclosporine A, delayed the removal of ERK and Akt phosphorylation under OGD. By comparing the extent of phosphorylation increase under OGD and normoxic conditions, we calculate that phosphatase activity was increased by approximately 3.6-fold during OGD. These data show that ATP levels control an important checkpoint in kinase function, and that ATP levels may need to be considered when studies of kinase function in relation to OGD are conducted.

Statistics

0200400'05'06'07'08'09'10'11'12'13'14'15'16'17
Citations per Year

520 Citations

Semantic Scholar estimates that this publication has 520 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Yung2003ErasureOK, title={Erasure of kinase phosphorylation in astrocytes during oxygen-glucose deprivation is controlled by ATP levels and activation of phosphatases.}, author={Hong wa Yung and Aviva M Tolkovsky}, journal={Journal of neurochemistry}, year={2003}, volume={86 5}, pages={1281-8} }