Increased expression of opioid delta receptors by deoxy conformation heme proteins in NG108-15 cells.
Increased expression of opioid delta receptors by deoxy conformation heme proteins in NG108-15 cells.
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NG108-15 细胞中脱氧构象血红素蛋白增加阿片 δ 受体的表达。
DOI：
10.1016/0006-8993(95)00089-9
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发表时间：
1995
期刊：
影响因子：
2.9
通讯作者：
Porreca,F
中科院分区：
文献类型：
--
作者：
Mayfield,KP;Horvath,R;Lai,J;Porreca,F
对长时间低氧的适应包括可能促进生存的蛋白质表达的增加。缺氧增加蛋白质表达的一种机制涉及到血红素蛋白质从氧化构象到去氧构象的变化。在目前的研究中，我们测试了用金属阳离子处理NG108-15细胞会增加增量阿片受体(DOR)表达的假设，金属阳离子已知会诱导血红素蛋白的脱氧构象。钴和镍诱导脱氧血红素蛋白构象，或锌作为对照，48h后定量检测DOR的表达。钴和镍，而不是锌，显著增加DOR的表达。血红素合成抑制剂会阻止钴取代的血红素蛋白的合成，这些蛋白被锁定在脱氧构象中。钴诱导的DOR表达增加可被血红素合成抑制剂4，6-二氧杂庚酸阻断。这些实验表明，被认为部分模拟缺氧的脱氧构象血红素蛋白增加了DOR的表达。DOR基因表达的增加提示DOR基因可能对低氧敏感。此外，DOR表达的增加提示了一种潜在的对低氧的适应策略，并可能是DOR表达生理调节的最早发现之一。
Adaptations to prolonged hypoxia include an increase in the expression of proteins that may facilitate survival. One mechanism by which hypoxia increases protein expression involves a change of heme proteins from oxygenated to deoxygenated conformations. In the present study, we tested the hypothesis that treatment of NG108-15 cells with metallic cations, which are known to induce a deoxygenated conformation of heme proteins, would increase delta opioid receptor (DOR) expression. Cells were treated with cobalt and nickel, which induce deoxygenated heme protein conformation, or zinc as a control for 48 h prior to quantifying DOR expression. Cobalt and nickel, but not zinc, significantly increased DOR expression. Heme synthesis inhibitors would block the synthesis of cobalt-substituted heme proteins which are locked in a deoxygenated conformation. The cobalt-induced increase in DOR expression was blocked by the heme synthesis inhibitor, 4,6-dioxoheptanoic acid. These experiments indicate that deoxygenated conformation heme proteins, which are thought to partially mimic hypoxia, increase DOR expression. The increase in DOR expression suggests that the DOR gene may be hypoxia-sensitive. Further, the increase in DOR expression suggests a potential adaptation strategy to hypoxia and may represent one of the first findings of physiological regulation of DOR expression.