Propofol Affects Neurodegeneration and Neurogenesis by Regulation of Autophagy via Effects on Intracellular Calcium Homeostasis.
Propofol Affects Neurodegeneration and Neurogenesis by Regulation of Autophagy via Effects on Intracellular Calcium Homeostasis.
复制标题
DOI：
10.1097/aln.0000000000001730
复制
发表时间：
2017-09
期刊：
影响因子：
8.8
通讯作者：
Wei H
中科院分区：
文献类型：
--
作者：
Qiao H;Li Y;Xu Z;Li W;Fu Z;Wang Y;King A;Wei H
在人皮质神经前体细胞中，我们研究了异丙酚对兰尼定和肌醇1，4，5-三磷酸钙释放通道钙稳态的影响。我们还研究了异丙酚对自噬、细胞存活以及神经和神经胶质形成的影响。研究了异丙酚在鼻咽癌中的剂量-反应关系。用四甲基偶氮唑蓝(3-(4，5-dimethylthiazol-2-yl)-2，5-diphenyltetrazolium)法和乳酸脱氢酶释放法检测细胞活力。用Fura-2检测丙泊酚对细胞内钙离子浓度的影响，用Western印迹法检测细胞自噬活性。用溴脱氧尿嘧啶核苷掺入和神经元、神经胶质细胞标记的免疫组织化学染色检测细胞的增殖和分化。异丙酚呈剂量和时间依赖性地诱导细胞损伤和Lc3II表达增加，以200μM作用24 h(67±11%，n=12~19)和6 h(2.4±0.5，对照组0.6±0.1，n=7)最为显著。2 0 0μM异丙酚处理后细胞内钙离子浓度也升高(34 6±71%，n=2 2~34)。10μM异丙酚刺激鼻咽癌增殖，促进神经细胞命运；200μM异丙酚抑制神经细胞增殖，促进神经胶质细胞命运(n=12~20)。与Ryanodine和肌醇1，4，5-三磷酸受体拮抗剂和抑制剂、胞内钙离子螯合剂或自噬抑制剂联合处理大多可减轻异丙酚对细胞存活、增殖和分化的影响。这些结果表明，异丙酚通过激活兰尼定和肌醇1，4，5-三磷酸受体对自噬的影响与异丙酚介导的细胞存活或神经再生密切相关。
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. The dose response relationship between propofol concentration and duration was studied in NPCs. 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. 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 NPC proliferation and promoted neuronal cell fate, while propofol at 200 μM impaired neuronal proliferation and promoted glial cell fate (n=12 to 20). Co-treatment with ryanodine and inositol 1, 4, 5-trisphosphate receptor antagonists and inhibitors, cytosolic Ca2+ chelators, or autophagy inhibitors mostly mitigated the propofol-mediated effects on survival, proliferation and differentiation. 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.
影响因子：
6.1
作者：
Li Q;Lu J;Wang X
通讯作者：
Wang X