The Mechanism of Oxidative Stress Stabilization of the Thromboxane Receptor in COS-7 Cells*
The Mechanism of Oxidative Stress Stabilization of the Thromboxane Receptor in COS-7 Cells*
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COS-7 细胞中血栓烷受体的氧化应激稳定机制*
DOI：
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发表时间：
2004
影响因子：
4.8
通讯作者：
J. Tippins
中科院分区：
文献类型：
--
作者：
F. Valentin;Mark C. Field;J. Tippins
8-异前列腺素F2α是一种在体内通过不依赖于环氧合酶的自由基催化的脂质过氧化产生的前列腺素类化合物，在氧化应激离体大鼠灌流心脏中作为血栓烷受体（TXA 2 R）的部分激动剂，是一种有效的血管收缩剂。我们推测，在离体心脏的反应可能是由于TXA 2 R密度的增加，这可能是由氧化自由基的存在引发的。以往的研究表明，血栓素A2受体密度增加，在动脉粥样硬化的中间和内膜平滑肌层在人类冠状动脉。在这里，我们描述了氧化应激对TXA 2 R的影响。COS-7细胞瞬时表达血栓素A2受体β（TXA 2 R β）。免疫荧光结果显示，H2 O2可促进TXA 2 R β从内质网向高尔基复合体的转位。H2 O2处理也增加了TXA 2 R拮抗剂（[3 H] SQ 29548）与膜的结合。蛋白质合成抑制剂放线菌酮处理后TXA 2 R β的降解动力学表明，TXA 2 R β不仅是一种主要定位于ER的短寿命蛋白质，而且TXA 2 R β的降解在H2 O2存在下受到调节。我们的研究结果表明，氧化应激可能通过胞内转位诱导TXA 2 R β蛋白的成熟和稳定。重要的是，这些观察结果还表明，TXA 2 R β水平受到ER相关降解的调节，并受到转运到ER后区室的效率的控制。通过从降解区室（即ER）易位来稳定TXA 2 R β可以解释体内观察到的受体密度增加。
The 8-iso-prostaglandin F2α, a prostanoid produced in vivo by cyclooxygenase-independent free-radical-catalyzed lipid peroxidation, acts as a partial agonist on the thromboxane receptor (TXA2R) and is a potent vasoconstrictor in the oxidatively stressed isolated perfused rat heart. We hypothesized that the response in the isolated heart may be due to augmentation of TXA2R density, which may be initiated by the presence of oxidative radicals. Previous studies have shown that TXA2R density is increased during atherosclerosis on both the medial and intimal smooth muscle layers in human coronary arteries. Here we describe the effect of oxidative stress on TXA2R. The thromboxane A2 receptor β isoform (TXA2Rβ) was transiently expressed in COS-7 cells. Immunofluorescence suggested that the presence of H2O2 increased translocation of TXA2Rβ from the endoplasmic reticulum (ER) to the Golgi complex. H2O2 treatment also increased binding of a TXA2R antagonist ([3H]SQ29548) to membranes. Degradation kinetics of TXA2Rβ following cycloheximide treatment, a protein synthesis inhibitor, suggested not only that TXA2Rβ is a short-lived protein predominantly localized to the ER but also that TXA2Rβ degradation is modulated in the presence of H2O2. Our results indicate that oxidative stress induces maturation and stabilization of the TXA2Rβ protein probably by intracellular translocation. Importantly, these observations also suggest that TXA2Rβ levels are modulated by ER-associated degradation and controlled by the efficiency of transport to post-ER compartments. Stabilization of the TXA2Rβ by translocation from a degradative compartment, i.e. the ER, can account for the augmentation of receptor density observed in vivo.
影响因子：
2.9
作者：
MORROW, JD;HARRIS, TM;ROBERTS, LJ
通讯作者：
ROBERTS, LJ
脂质连接寡糖的延伸是未折叠蛋白质反应的一个高度优先的方面：I型先天性糖基化成纤维细胞疾病中的内质网应激。
影响因子：
4.3
作者：
Shang,Jie;Körner,Christian;Freeze,Hudson;Lehrman,MarkA
通讯作者：
Lehrman,MarkA
CFTR 的生物合成和降解。
DOI：
10.1152/physrev.1999.79.1.s167
发表时间：
1999
期刊：
Physiological reviews.
影响因子：
--
作者：
Kopito,RR
通讯作者：
Kopito,RR