Hypoxic preconditioning suppresses group III secreted phospholipase A2-induced apoptosis via JAK2-STAT3 activation in cortical neurons

Authors: Wang, Guansong¹; Zhou, Deshan²; Wang, Changzheng¹; Gao, Yuqi²; Zhou, Qiquan²; Qian, Guisheng¹; DeCoster, Mark A.³

Source: Journal of Neurochemistry, Volume 114, Number 4, August 2010 , pp. 1039-1048(10)

Publisher: Wiley-Blackwell

Abstract:

J. Neurochem. (2010) 114, 1039-1048. Abstract

Our previous studies show that group III secreted phospholipases A₂ (sPLA₂s III) induces extensive neuronal apoptosis in brain cortical cultures. However, the molecular mechanisms underlying sPLA₂ III-induced neuronal injury/death are still unknown. Also it is not clear whether hypoxic pre-conditioning (HPC) is able to protect neurons from the sPLA₂ III insult. In this report, we demonstrate that sPLA₂ III significantly decreased production of Bcl-xl and the ratio of Bcl-xl/Bax, and increased expression of Bax, cleaved caspase 3, and cleaved α-Fodrin in primary neuronal culture. HPC prevented the sPLA₂ III-induced decreases in production of Bcl-xl and the ratio of Bcl-xl/Bax, and increases in expression of Bax, cleaved caspase 3, and α-Fodrin. However, the HPC-produced neuronal protection was eliminated or attenuated by AG490, rapamycin, and STAT3 shRNA. Our results suggest that sPLA₂ III-induced neuronal apoptosis is likely because of its alterations in expression and activity of Bcl-xl, Bax, caspase 3, and its target gene fodrin; and that HPC-produced neuroprotection against the sPLA₂ III toxicity is mediated via JAK-STAT signal pathways that regulate the expression of Bcl-xl, Bax, and cleaved caspase 3 in cultured cortical neurons.

Keywords: anoxia; cortical neurons; JAK2; pre-conditioning; secreted phospholipase A2; STAT3

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1471-4159.2010.06817.x

Affiliations: 1: Institute of Respiratory Diseases in Second affiliated Hospital, The Third Military Medical University of China, Chongqing, China 2: Department of Neuroscience, Histology and Altitude Military Medicine, The Third Military Medical University of China, Chongqing, China 3: Biomedical Engineering and Institute for MicroManufacturing, Louisiana Tech University, Ruston, Louisiana, USA

Publication date: 2010-08-01

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• In this Subject: Anatomy & Physiology
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