Inhalational anesthetics induce cell damage by disruption of intracellular calcium homeostasis with different potencies.
Inhalational anesthetics induce cell damage by disruption of intracellular calcium homeostasis with different potencies.
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DOI：
10.1097/aln.0b013e31817f5c47
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发表时间：
2008-08
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：
Yang H;Liang G;Hawkins BJ;Madesh M;Pierwola A;Wei H
我们假设吸入麻醉剂通过过度激活肌醇1，4，5-三磷酸（IP 3）受体引起内质网异常钙释放而诱导细胞损伤，异氟烷的效力大于七氟烷或地氟烷。我们用异氟醚、七氟醚和地氟醚等剂量暴露处理IP 3受体完全敲除的DT 40鸡B淋巴细胞或其相应的野生型对照细胞。然后，我们通过计数膜联蛋白V或碘化丙啶阳性染色细胞的百分比或测量半胱天冬酶-3活性来确定细胞损伤的程度。我们还研究了在两种类型的DT 40细胞中，等浓度的异氟醚、七氟醚和地氟醚引起的内质网、胞浆和线粒体中钙离子浓度的变化。长时间使用2种最小肺泡浓度的七氟烷或地氟烷（24 h）仅在DT 40野生型中诱导显著的细胞损伤，但在IP 3受体完全敲除细胞中未诱导显著的细胞损伤，但效力显著低于异氟烷。根据，所有三种吸入麻醉剂诱导内质网中的钙浓度的显着降低，伴随着随后的显着增加，在细胞质和线粒体钙浓度仅在DT 40野生型，而不是在IP 3受体总敲除细胞。异氟烷治疗显示出比七氟烷或地氟烷显著更大的效应效力。吸入性麻醉剂可通过过度激活IP 3受体引起内质网异常钙释放而诱导细胞损伤。异氟烷比七氟烷或地氟烷更能引起钙从内质网释放并诱导细胞损伤。
We hypothesized that inhalational anesthetics induced cell damage by causing abnormal calcium release from the endoplasmic reticulum via excessive activation of inositol 1,4,5-trisphosphate (IP3) receptors, with isoflurane greater potency than sevoflurane or desflurane. We treated DT40 chicken B lymphocytes with total IP3 receptor knock-out or their corresponding wild type control cells with equipotent exposure of isoflurane, sevoflurane and desflurane. We then determined the degree of cell damage by counting the percentage of annexin V or propidium iodide positively stained cells or measuring caspase-3 activity. We also studied the changes of calcium concentrations in the endoplasmic reticulum, cytosol and mitochondria evoked by equipotent concentrations of isoflurane, sevoflurane and desflurane in both types of DT40 cells. Prolonged use of 2 minimal alveolar concentration sevoflurane or desflurane (24 hr) induced significant cell damage only in DT40 Wild type but not IP3 receptor total knock-out cells, but with significantly less potency than isoflurane. In accordance, all three inhalational anesthetics induced significant decrease of calcium concentrations in the endoplasmic reticulum, accompanied with a subsequent significant increase in the cytosol and mitochondrial calcium concentrations only in DT40 wild type but not in IP3 receptor total knock-out cells. Isoflurane treatment showed significantly greater potency of effect than sevoflurane or desflurane. Inhalational anesthetics may induce cell damage by causing abnormal calcium release from the endoplasmic reticulum via excessive activation of IP3 receptors. Isoflurane has greater potency than sevoflurane or desflurane to cause calcium release from the endoplasmic reticulum and to induce cell damage.