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Neurochemical Research

, Volume 32, Issue 12, pp 2160–2166 | Cite as

p38α MAP Kinase Mediates Hypoxia-Induced Motor Neuron Cell Death: A Potential Target of Minocycline’s Neuroprotective Action

  • Guiwen Guo
  • Narayan R. BhatEmail author
Original Paper

Abstract

Hypoxia-ischemia (HI) may play a significant role in motor neuron death associated with the pathology of spinal cord injury and, perhaps, amyotrophic lateral sclerosis. The present study employs an in vitro model of HI to investigate the role of a stress kinase pathway, i.e., p38 MAP kinase, in cell death signaling in a motor neuron cell line, i.e., NSC34, subjected to oxygen-glucose deprivation (OGD). Although the neurons were essentially tolerant to either hypoxia (0.2% O2) or low glucose (1 mM) alone, more than 60% of them died in response to combined low oxygen and low-glucose exposure. Minocycline, a semi-synthetic tetracycline known for its neuroprotective effects in models of neurodegeneration, afforded substantial (∼50%) protection against hypoxic cell death, assessed by lactate dehydrogenase release and flow cytometry, while suppressing OGD-induced p38 MAP kinase activation. An inhibitor of p38 kinase, SB203580, as well as siRNA-mediated down-regulation of p38 kinase elicited an almost complete blockade of OGD-induced cell death. The use of p38 isoform-specific siRNAs further revealed preferential involvement of the α over the β isoform of p38 MAP kinase in hypoxic neuronal cell death in our model.

Keywords

Hypoxia-ischemia Oxygen-glucose deprivation Motor neuron Cell death p38 MAP kinase isoform Minocycline 

Notes

Acknowledgment

This work was supported by NIA grant P01 AG 023630 and a pilot grant from South Carolina spinal cord injury research fund.

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Department of NeurosciencesMedical University of South CarolinaCharlestonUSA

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