論文 - 詳細
| RRC ID | 66001 |
|---|---|
| 著者 | Ren G, Zhou Y, Liang G, Yang B, Yang M, King A, Wei H. |
| タイトル | General Anesthetics Regulate Autophagy via Modulating the Inositol 1,4,5-Trisphosphate Receptor: Implications for Dual Effects of Cytoprotection and Cytotoxicity. |
| ジャーナル | Sci Rep |
| Abstract |
General anesthetics are both neuroprotective and neurotoxic with unclear mechanisms. General anesthetics may control cell survival via their effects on autophagy by activation of type 1 inositol triphosphate receptor (InsP3R-1). DT40 or SH-SY5Y cells with only or over 99% expression of InsP3R-1 were treated with isoflurane or propofol. Cell viability was determined by MTT reduction or LDH release assays. Apoptosis was determined by measuring Caspase-3 or by TUNEL assay. Autophagy activity was determined by measuring LC3 II and P62. We evaluated mitochondrial integrity using MitoTracker Green and cytosolic ATP levels. Fura2-AM was used to measure the concentrations of cytosolic calcium ([Ca2+]c). Propofol significantly increased peak and integrated calcium response (P < 0.001) in cells with InsP3R-1 but not in cells with triple knockout of InsP3R. Both propofol and isoflurane increased autophagy induction (P < 0.05) in an mTOR- and InsP3R- activity dependent manner. Short exposure to propofol adequately activated InsP3-1 to provide sufficient autophagy for cytoprotection, while prolonged exposure to propofol induced cell apoptosis via impairment of autophagy flux through over activation of InsP3-1. Propofol damaged mitochondria and decreased cytosolic ATP. The effects of general anesthetics on apoptosis and autophagy are closely integrated; both are caused by differential activation of the type 1 InsP3R. |
| 巻・号 | 7(1) |
| ページ | 12378 |
| 公開日 | 2017-9-28 |
| DOI | 10.1038/s41598-017-11607-0 |
| PII | 10.1038/s41598-017-11607-0 |
| PMID | 28959036 |
| PMC | PMC5620053 |
| MeSH | Anesthetics, General / pharmacology* Animals Apoptosis / drug effects Autophagy / drug effects* Caspase 3 / metabolism Cell Line Chickens Cytoprotection / drug effects* Humans Inositol 1,4,5-Trisphosphate Receptors / metabolism* Lymphocytes Neural Stem Cells Neurotoxicity Syndromes / etiology Neurotoxicity Syndromes / pathology* Propofol / pharmacology |
| IF | 3.998 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | IP3R^(-) DT40(RCB1467) |