| 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
|
| リソース情報 |
| ヒト・動物細胞 |
IP3R^(-) DT40(RCB1467) |
