title: Hypoxic preconditioning suppresses group III secreted phospholipase A2-induced apoptosis via JAK2-STAT3 activation in cortical neurons.
abstract: Our previous studies show that group III secreted phospholipases A(2) (sPLA(2)s III) induces extensive neuronal apoptosis in brain cortical cultures. However, the molecular mechanisms underlying sPLA(2) 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 sPLA(2) III insult. In this report, we demonstrate that sPLA(2) III significantly decreased production of Bcl-xl and the ratio of Bcl-xl/Bax, and increased expression of Bax, cleaved caspase 3, and cleaved alpha-Fodrin in primary neuronal culture. HPC prevented the sPLA(2) 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 alpha-Fodrin. However, the HPC-produced neuronal protection was eliminated or attenuated by AG490, rapamycin, and STAT3 shRNA. Our results suggest that sPLA(2) 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 sPLA(2) 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.
authors.affiliation: Institute of Respiratory Diseases in Second affiliated Hospital, The Third Military Medical University of China, Chongqing, China. wanggs2003@hotmail.com
authors.forename: Guansong
authors.initials: G
authors.lastname: Wang
authors.forename: Deshan
authors.initials: D
authors.lastname: Zhou
authors.forename: Changzheng
authors.initials: C
authors.lastname: Wang
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Gao
authors.forename: Qiquan
authors.initials: Q
authors.lastname: Zhou
authors.forename: Guisheng
authors.initials: G
authors.lastname: Qian
authors.forename: Mark A
authors.initials: MA
authors.lastname: DeCoster
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D054520:Group III Phospholipases A2 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D020925:Hypoxia-Ischemia, Brain / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D019194:Ischemic Preconditioning / Q000379:methods; D053614:Janus Kinase 2 / Q000378:metabolism*; D009410:Nerve Degeneration / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D009474:Neurons / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D051017:Apoptosis Regulatory Proteins; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; D054520:Group III Phospholipases A2