The protective effect of propofol against TNF-α-induced apoptosis was mediated via inhibiting iNOS/NO production and maintaining intracellular Ca2+ homeostasis in mouse hippocampal HT22 cells

作者：Xu, Zheng; Lu, Yan; Wang, Jiaqiang; Ding, Xiaowei; Chen, Jiawei^*; Miao, Changhong^*

来源：Biomedicine & Pharmacotherapy, 2017, 91: 664-672.

DOI：10.1016/j.biopha.2017.04.110

• Anesthetics i.v.
• Propofol
• Neuroinflammation
• Apoptosis

Aim: Inflammation cytokine tumor necrosis factor-alpha (TNF-alpha) induces apoptosis in neuronal cells. We hypothesized that propofol may attenuate TNF-alpha-induced apoptosis in mouse hippocampal HT22 cells and aimed to explore the underlying mechanisms. @@@ Methods: Mouse hippocampal HT22 cells were pretreated with propofol, and then stimulated with TNF alpha. Cell viability was measured by cell counting kit 8 (CCK8). Cell apoptosis was examined by flow cytometry analysis. The effect of propofol on TNF-alpha-modulated nitric oxide production was measured by a nitrate reductase assay kit, intracellular calcium release and mitochondrial membrane potential (MMP) depolarization were measured by flow cytometry analysis, and the expression of inducible nitric oxide synthase (iNOS), C/EBP homologous protein (CHOP), B-cell lymphoma 2 (Bcl2) family and caspases were detected by Western blot. @@@ Results: Compared with control, TNF-a concentration-and time-dependently increased HT22 cell apoptosis, which was attenuated by 25 mu mol/l propofol. TNF-alpha (40 ng/ml, 24 h) induced the overexpression of iNOS and the release of nitric oxide, caused the accumulation of intracellular Ca2+ and endoplasmic reticulum (ER) stress, and therefore leading to mitochondrial dysfunction. Importantly, these effects were alleviated by 25 mu mol/l propofol. @@@ Conclusions: We demonstrated that propofol could attenuate TNF-alpha-induced HT22 apoptosis. More importantly, we indicated that the underlying mechanism may involve iNOS/NO, Ca2+ and mitochondrial dysfunction.

• 出版日期2017-7
• 单位复旦大学