Hypoxic preconditioning suppresses group III secreted phospholipase A2-induced apoptosis via JAK2-STAT3 activation in cortical neurons.
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.
Wang
Guansong
G
Institute of Respiratory Diseases in Second affiliated Hospital, The Third Military Medical University of China, Chongqing, China. wanggs2003@hotmail.com
Zhou
Deshan
D
Wang
Changzheng
C
Gao
Yuqi
Y
Zhou
Qiquan
Q
Qian
Guisheng
G
DeCoster
Mark A
MA
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
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