Hui Qiao1, Yun Li, Zhendong Xu, Wenxian Li, Zhijian Fu, Yuezhi Wang, Alexander King, Huafeng Wei. 1. From the Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (H.Q., Y.L., Z.X., A.K., H.W.); Department of Anesthesiology, The Eye Ear Nose and Throat Hospital of Fudan University, Shanghai, People's Republic of China (H.Q., W.L.); Department of Pain Medicine, Provincial Hospital Affiliated with Shandong University, Jinan, People's Republic of China (Y.L., Z.F.); Department of Anesthesiology, First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China (Z.X.); and Department of Gerontology, Huashan Hospital of Fudan University, Shanghai, People's Republic of China (Y.W.).
Abstract
BACKGROUND: In human cortical neural progenitor cells, we investigated the effects of propofol on calcium homeostasis in both the ryanodine and inositol 1,4,5-trisphosphate calcium release channels. We also studied propofol-mediated effects on autophagy, cell survival, and neuro- and gliogenesis. METHODS: The dose-response relationship between propofol concentration and duration was studied in neural progenitor cells. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase release assays. The effects of propofol on cytosolic calcium concentration were evaluated using Fura-2, and autophagy activity was determined by LC3II expression levels with Western blot. Proliferation and differentiation were evaluated by bromodeoxyuridine incorporation and immunostaining with neuronal and glial markers. RESULTS: Propofol dose- and time-dependently induced cell damage and elevated LC3II expression, most robustly at 200 µM for 24 h (67 ± 11% of control, n = 12 to 19) and 6 h (2.4 ± 0.5 compared with 0.6 ± 0.1 of control, n = 7), respectively. Treatment with 200 μM propofol also increased cytosolic calcium concentration (346 ± 71% of control, n = 22 to 34). Propofol at 10 µM stimulated neural progenitor cell proliferation and promoted neuronal cell fate, whereas propofol at 200 µM impaired neuronal proliferation and promoted glial cell fate (n = 12 to 20). Cotreatment with ryanodine and inositol 1,4,5-trisphosphate receptor antagonists and inhibitors, cytosolic Ca chelators, or autophagy inhibitors mostly mitigated the propofol-mediated effects on survival, proliferation, and differentiation. CONCLUSIONS: These results suggest that propofol-mediated cell survival or neurogenesis is closely associated with propofol's effects on autophagy by activation of ryanodine and inositol 1,4,5-trisphosphate receptors.
BACKGROUND: In human cortical neural progenitor cells, we investigated the effects of propofol on calcium homeostasis in both the ryanodine and inositol 1,4,5-trisphosphate calcium release channels. We also studied propofol-mediated effects on autophagy, cell survival, and neuro- and gliogenesis. METHODS: The dose-response relationship between propofol concentration and duration was studied in neural progenitor cells. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase release assays. The effects of propofol on cytosolic calcium concentration were evaluated using Fura-2, and autophagy activity was determined by LC3II expression levels with Western blot. Proliferation and differentiation were evaluated by bromodeoxyuridine incorporation and immunostaining with neuronal and glial markers. RESULTS:Propofol dose- and time-dependently induced cell damage and elevated LC3II expression, most robustly at 200 µM for 24 h (67 ± 11% of control, n = 12 to 19) and 6 h (2.4 ± 0.5 compared with 0.6 ± 0.1 of control, n = 7), respectively. Treatment with 200 μM propofol also increased cytosolic calcium concentration (346 ± 71% of control, n = 22 to 34). Propofol at 10 µM stimulated neural progenitor cell proliferation and promoted neuronal cell fate, whereas propofol at 200 µM impaired neuronal proliferation and promoted glial cell fate (n = 12 to 20). Cotreatment with ryanodine and inositol 1,4,5-trisphosphate receptor antagonists and inhibitors, cytosolic Ca chelators, or autophagy inhibitors mostly mitigated the propofol-mediated effects on survival, proliferation, and differentiation. CONCLUSIONS: These results suggest that propofol-mediated cell survival or neurogenesis is closely associated with propofol's effects on autophagy by activation of ryanodine and inositol 1,4,5-trisphosphate receptors.
Authors: Matthew L Pearn; Yue Hu; Ingrid R Niesman; Hemal H Patel; John C Drummond; David M Roth; Katerina Akassoglou; Piyush M Patel; Brian P Head Journal: Anesthesiology Date: 2012-02 Impact factor: 7.892
Authors: George K Istaphanous; Jennifer Howard; Xinyu Nan; Elizabeth A Hughes; John C McCann; John J McAuliffe; Steve C Danzer; Andreas W Loepke Journal: Anesthesiology Date: 2011-03 Impact factor: 7.892
Authors: Daqing Ma; Mahmuda Hossain; Garry K J Pettet; Yan Luo; Ta Lim; Stanislav Akimov; Robert D Sanders; Nicholas P Franks; Mervyn Maze Journal: J Cereb Blood Flow Metab Date: 2006-02 Impact factor: 6.200
Authors: Jeffrey W Sall; Greg Stratmann; Jason Leong; William McKleroy; Daniel Mason; Shanti Shenoy; Samuel J Pleasure; Phillip E Bickler Journal: Anesthesiology Date: 2009-04 Impact factor: 7.892
Authors: Jun Fan; Quan Zhou; Yan Li; Xiuling Song; Jijie Hu; Zaisheng Qin; Jing Tang; Tao Tao Journal: Front Mol Neurosci Date: 2018-03-23 Impact factor: 5.639