Zheng Xu1, Yan Lu2, Jiaqiang Wang3, Xiaowei Ding4, Jiawei Chen5, Changhong Miao6. 1. Department of Anesthesiology, Fudan University Shanghai Cancer Centre, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China. Electronic address: anesthesiology2016@126.com. 2. Department of Anesthesiology, Fudan University Shanghai Cancer Centre, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China. Electronic address: aneyan_lu@163.com. 3. Department of Anesthesiology, Fudan University Shanghai Cancer Centre, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China. Electronic address: anesthesiologylu@hotmail.com. 4. Department of Anesthesiology, Fudan University Shanghai Cancer Centre, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China. Electronic address: ane_minmin@163.com. 5. Department of Anesthesiology, Fudan University Shanghai Cancer Centre, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China. Electronic address: jiawei_chen@hotmail.com. 6. Department of Anesthesiology, Fudan University Shanghai Cancer Centre, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China. Electronic address: anesthesiology_mp@126.com.
Abstract
AIM: Inflammation cytokine tumor necrosis factor-α (TNF-α) induces apoptosis in neuronal cells. We hypothesized that propofol may attenuate TNF-α-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-α. Cell viability was measured by cell counting kit 8 (CCK8). Cell apoptosis was examined by flow cytometry analysis. The effect of propofol on TNF-α-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-α concentration- and time-dependently increased HT22 cell apoptosis, which was attenuated by 25μmol/l propofol. TNF-α (40ng/ml, 24h) 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 25μmol/l propofol. CONCLUSIONS: We demonstrated that propofol could attenuate TNF-α-induced HT22 apoptosis. More importantly, we indicated that the underlying mechanism may involve iNOS/NO, Ca2+ and mitochondrial dysfunction.
AIM: Inflammation cytokine tumor necrosis factor-α (TNF-α) induces apoptosis in neuronal cells. We hypothesized that propofol may attenuate TNF-α-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-α. Cell viability was measured by cell counting kit 8 (CCK8). Cell apoptosis was examined by flow cytometry analysis. The effect of propofol on TNF-α-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-α concentration- and time-dependently increased HT22 cell apoptosis, which was attenuated by 25μmol/l propofol. TNF-α (40ng/ml, 24h) 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 25μmol/l propofol. CONCLUSIONS: We demonstrated that propofol could attenuate TNF-α-induced HT22 apoptosis. More importantly, we indicated that the underlying mechanism may involve iNOS/NO, Ca2+ and mitochondrial dysfunction.