Intracellular Ca2+ homeostasis and JAK1/STAT3 pathway are involved in the protective effect of propofol on BV2 microglia against hypoxia-induced inflammation and apoptosis.

Abstract

BACKGROUND:

Perioperative hypoxia may induce microglial inflammation and apoptosis, resulting in brain injury. The neuroprotective effect of propofol against hypoxia has been reported, but the underlying mechanisms are far from clear. In this study, we explored whether and how propofol could attenuate microglia BV2 cells from CoCl2-induced hypoxic injury.

METHODS:

Mouse microglia BV2 cells were pretreated with propofol, and then stimulated with CoCl2. TNF-α level in the culture medium was measured by ELISA kit. Cell apoptosis and intracellular calcium concentration were measured by flow cytometry analysis. The effect of propofol on CoCl2-modulated expression of Ca2+/Calmodulin (CaM)-dependent protein kinase II (CAMKIIα), phosphorylated CAMKIIα (pCAMKIIα), STAT3, pSTAT3Y705, pSTAT3S727, ERK1/2, pERK1/2, pNFκB(p65), pro-caspase3, cleaved caspase 3, JAK1, pJAK1, JAK2, pJAK2 were detected by Western blot.

RESULTS:

In BV2 cell, CoCl2 treatment time-dependently increased TNF-α release and induced apoptosis, which were alleviated by propofol. CoCl2 (500μmol/L, 8h) treatment increased intracellular Ca2+ level, and caused the phosphorylation of CAMKIIα, ERK1/2 and NFκB (p65), as well as the activation of caspase 3. More importantly, these effects could be modulated by 25μmol/L propofol via maintaining intracellular Ca2+ homeostasis and via up-regulating the phosphorylation of JAK1 and STAT3 at Tyr705.

CONCLUSION:

Propofol could protect BV2 microglia from hypoxia-induced inflammation and apoptosis. The potential mechanisms may involve the maintaining of intracellular Ca2+ homeostasis and the activation of JAK1/STAT3 pathway.

• Authors: Yan Lu, Yuechao Gu, Xiaowei Ding, Jiaqiang Wang, Jiawei Chen, Changhong Miao
• Journal: PloS one (PLoS One) Vol. 12 Issue 5 Pg. e0178098 ( 2017) ISSN: 1932-6203 [Electronic] United States
• PMID: 28542400 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Cations, Divalent
• Neuroprotective Agents
• STAT3 Transcription Factor
• Stat3 protein, mouse
• Tumor Necrosis Factor-alpha
• Cobalt
• Jak1 protein, mouse
• Janus Kinase 1
• cobaltous chloride
• Calcium
• Propofol

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Apoptosis (drug effects, physiology)
• Calcium (metabolism)
• Cations, Divalent (metabolism)
• Cell Hypoxia (drug effects, physiology)
• Cell Line
• Cobalt (toxicity)
• Drug Evaluation, Preclinical
• Intracellular Space (drug effects, metabolism)
• Janus Kinase 1 (metabolism)
• Mice
• Microglia (drug effects, enzymology, immunology)
• Neuroimmunomodulation (drug effects, physiology)
• Neuroprotective Agents (pharmacology)
• Phosphorylation (drug effects)
• Propofol (pharmacology)
• STAT3 Transcription Factor (metabolism)
• Signal Transduction (drug effects)
• Tumor Necrosis Factor-alpha (metabolism)