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Expression of Hypoxia Inducible Factor 1alpha Is Protein Kinase A-dependent in Primary Cortical Astrocytes Exposed to Severe Hypoxia

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Abstract

The hypoxia inducible factor 1 (HIF-1) and the cyclic AMP-responsive element binding protein (CREB) are two transcription factors that have been studied in the context of neuronal survival and neurodegeneration. HIF-1 upregulation and CREB activation have been observed not only in neurons but also in astrocytes under conditions of hypoxia. We hypothesized that activation of CREB regulate HIF-1α expression in the nucleus of cortical astrocytes under in vitro ischemic condition. To test the hypothesis, we determined the effects of inhibiting the CREB activation pathway on the expression of HIF-1α protein in astrocytes exposed to CoCl2 and severe hypoxia (near anoxia, 0.1% O2). The results demonstrated that inhibition of CaMKII and CaMKIV had no effect on both HIF-1α and pCREB expression in cortical astrocytes exposed to CoCl2 and anoxia. In contrast, PKA inhibition lowered the expression of HIF-1α and pCREB expression. Furthermore, the inhibition of PKA but not CaMKII or CaMKIV increased cell death of astrocytes exposed to near anoxia. The results suggest that PKA plays an important role in the cell survival signaling pathways in astrocytes.

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Acknowledgements

This work was supported by in part by KUCR. The authors gratefully thank Ms. Cristina Parra for proofreading the manuscript and Ms. Jiani Chen for the artwork.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, KS, 66045, USA

    Prabhu Ramamoorthy & Honglian Shi

  2. Department of Anesthesiology, School of Medicine, University of Kansas, Kansas City, KS, 66160, USA

    Grace Xu

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  1. Prabhu Ramamoorthy
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Correspondence to Honglian Shi.

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Ramamoorthy, P., Xu, G. & Shi, H. Expression of Hypoxia Inducible Factor 1alpha Is Protein Kinase A-dependent in Primary Cortical Astrocytes Exposed to Severe Hypoxia. Neurochem Res 44, 258–268 (2019). https://doi.org/10.1007/s11064-018-2516-9

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  • DOI: https://doi.org/10.1007/s11064-018-2516-9

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