Role of nitrite, a nitric oxide derivative, in K-Cl cotransport activation of low-potassium sheep red blood cells
Role of nitrite, a nitric oxide derivative, in K-Cl cotransport activation of low-potassium sheep red blood cells
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DOI：
10.1007/s002329900457
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发表时间：
1998-12-01
影响因子：
2.4
通讯作者：
Lauf, PK
中科院分区：
文献类型：
--
作者：
Adragna, NC;Lauf, PK
K-Cl共转运（COT）是K和Cl的耦合运动，存在于大多数细胞中，与调节性体积减少相关，易受氧化影响，在镰状细胞贫血中功能性过表达。本研究的目的是表征氧化剂亚硝酸盐（NO2-）对氯化钾COT的影响。NO2-是短寿命高活性自由基一氧化氮（NO）的稳定代谢终产物，是离子通道的氧化剂和调节剂，也是血管扩张剂。在某些系统中，对NO2-的反应与NO的反应相同。我们假设NO2-激活K-Cl GOT。低钾（LK）绵羊红细胞（SRBC）被用作模型。研究了不同浓度（10（-6）~ 10（-1）M）的NaNO 2对低渗Cl和NO3介质中钾外流、Cl依赖性钾外流（K-Cl COT）、谷胱甘肽（GSH）和高铁血红蛋白（MetHb）形成的影响。在支持我们的假设，钾外流和氯化钾COT刺激浓度增加的NaNO 2。钾外流的刺激依赖于外部Cl，并表现出滞后期，通过调节机制与K-Cl COT的激活一致。LK SRBC暴露于NaNO 2降低GSH，巯基氧化剂的效应特征，并诱导MetHb形成。K-Cl COT活性与Methb形成呈正相关。N-乙基-马来酰亚胺（NEM）是一种有效的K-Cl COT激活剂，用于评估NO作用的机制。结果表明，NEM和NO2-利用至少一个共同的途径K-Cl COT激活。由于NaNO 2也是一种众所周知的血管扩张剂，目前的研究结果表明K-Cl COT在血管扩张中的作用。
K-Cl cotransport (COT) is the coupled movement of K and Cl, present in most cells, associated with regulatory volume decrease, susceptible to oxidation and functionally overexpressed in sickle cell anemia. The aim of this study was to characterize the effect of the oxidant nitrite (NO2-) on K-Cl COT. NO2- is a stable metabolic end product of the short-lived highly reactive free radical nitric oxide (NO), an oxidant and modulator of ion channels, and a vasodilator. In some systems, the response to NO2- is identical to that of NO. We hypothesized that NO2- activates K-Cl GOT. Low potassium (LK) sheep red blood cells (SRBCs) were used as a model. The effect of various concentrations (10(-6) to 10(-1) M) of NaNO2 was studied on K efflux in hypotonic Cl and NO3 media, Cl-dependent K efflux (K-Cl COT), glutathione (GSH), and methemoglobin (MetHb) formation. In support of our hypothesis, K efflux and K-Cl COT were stimulated by increasing concentrations of NaNO2. Stimulation of K efflux was dependent upon external Cl and exhibited a lag phase, consistent with activation of K-Cl COT through a regulatory mechanism. Exposure of LK SRBCs to NaNO2 decreased GSH, an effect characteristic of a thioloxidizing agent, and induced MetHb formation. K-Cl COT activity was positively correlated with Methb formation. N-ethyl-maleimide (NEM), a potent activator of K-Cl COT, was used to assess the mechanism of NO,action. The results suggest that NEM and NO2- utilize at least one common pathway for K-Cl COT activation. Since NaNO2 is also a well known vasodilator, the present findings suggest a role of K-Cl COT in vasodilation.