Vareesangthip Kriengsak, Panthongdee Weerawat, Shayakul Chairat, Nitiyanant Wannee, Ong-Aj-Yooth Leena
Renal Division, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkoknoi, Bangkok, Thailand.
J Med Assoc Thai. 2006 Aug;89 Suppl 2:S48-53.
In essential hypertension and diabetic nephropathy, sodium-lithium counter transport (Na/Li CT) is an inherited marker for metabolic influences of cardiovascular risk. The kinetics of Na/Li CT are modified by two types of thiol group in the membrane. In choline medium, the type 1 thiol reacts with N-ethtyl maleimide (NEM) to cause a decrease in Km and increase Vmax/Km ratio. However in the presence of external Na or Li both the type 1 or type 2 thiols react so that both Km and Vmax are reduced. Low Km of Na/Li CT has been previously reported to be a major abnormality in diabetic nephropathy (DN) and can be used to identify diabetic patients who are at high risk for DN. A recent study showed that the type 1 thiol protein controlling the Km of Na/Li CT was a 33-kD protein and the gene for this protein is going to be cloned.
The authors sought to identify Na/Li CT kinetic abnormalities in Type 2 diabetes in Thai patients.
Erythrocyte Na/Li CT kinetics and their modulation by thiol proteins were measured in erythrocytes from 22 patients with Type 2 diabetes and 42 normal control subjects.
The kinetics of Na/Li CT in untreated erythrocytes were similar Thiol protein alkylation with NEM generally caused both Vmax and Km to fall, but caused Km to rise in erythrocytes of diabetic patients, whose native Km was low. Thus, abnormalities in the regulation of Na/Li CT by key thiol proteins were found in about one-third of subjects with Type 2 diabetes in Thailand.
Membrane abnormalities may indicate a common pathway of pathological mechanism found in essential hypertension and diabetic nephropathy and may be used as a phenotype for further genetic studies of this transporter.
在原发性高血压和糖尿病肾病中，钠-锂逆向转运（Na/Li CT）是心血管风险代谢影响的一种遗传标志物。Na/Li CT的动力学受膜中两种类型的硫醇基团调节。在胆碱介质中，1型硫醇与N-乙基马来酰亚胺（NEM）反应，导致Km降低，Vmax/Km比值增加。然而，在存在外部钠或锂的情况下，1型或2型硫醇都会发生反应，从而使Km和Vmax都降低。先前报道，Na/Li CT的低Km是糖尿病肾病（DN）的主要异常表现，可用于识别患DN风险高的糖尿病患者。最近一项研究表明，控制Na/Li CT的Km的1型硫醇蛋白是一种33-kD蛋白，该蛋白的基因即将被克隆。
作者试图确定泰国2型糖尿病患者中Na/Li CT的动力学异常。
测量了22例2型糖尿病患者和42例正常对照者红细胞中的红细胞Na/Li CT动力学及其受硫醇蛋白的调节情况。
未经处理的红细胞中Na/Li CT的动力学相似。用NEM对硫醇蛋白进行烷基化处理通常会导致Vmax和Km均下降，但在天然Km较低的糖尿病患者红细胞中会导致Km升高。因此，在泰国约三分之一的2型糖尿病患者中发现了关键硫醇蛋白对Na/Li CT调节的异常。
膜异常可能表明原发性高血压和糖尿病肾病中存在共同的病理机制途径，并且可作为该转运体进一步基因研究的一种表型。
