• Hui Qiao, Yun Li, Zhendong Xu, Wenxian Li, Zhijian Fu, Yuezhi Wang, Alexander King, and Huafeng Wei.
• 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.).
• Anesthesiology. 2017 Sep 1; 127 (3): 490-501.

BackgroundIn 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.MethodsThe 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.ResultsPropofol 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.ConclusionsThese 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.

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