患有微血管病变的2型糖尿病患者中谷胱甘肽化血红蛋白（HbSSG）增加。

Increased glutathionylated hemoglobin (HbSSG) in type 2 diabetes subjects with microangiopathy.

作者信息

Sampathkumar Rangasamy, Balasubramanyam Muthuswamy, Sudarslal Sadasivannair, Rema Mohan, Mohan Viswanthan, Balaram Padmanabhan

机构信息

Department of Cell and Molecular Biology, Madras Diabetes Research Foundation, 6B, Conran Smith Road, Gopalapuram, Chennai-600 086, India.

出版信息

Clin Biochem. 2005 Oct;38(10):892-9. doi: 10.1016/j.clinbiochem.2005.06.009.

DOI:10.1016/j.clinbiochem.2005.06.009

PMID:16051210

Abstract

OBJECTIVE

Protein glutathionylation is considered an important post-translational modification in the pathogenesis of complex diseases. The aim of this study was to examine whether hemoglobin (Hb) is modified by reduced glutathione (GSH) via oxidation of the thiol groups present in diabetes and its associated microangiopathy and to determine whether oxidative imbalance has any correlation with glutathionylated Hb (HbSSG) levels.

METHODS

The study group consisted of a total of 130 subjects which included non-diabetic healthy control subjects (n = 30) and type 2 diabetic patients with (n = 53) and without (n = 47) microangiopathy. All subjects were assessed for glycemic and lipidemic status, while diabetic subjects were also assessed for the diagnosis of retinopathy and nephropathy. RBC lysates from all the subjects were analyzed by liquid chromatography/electrospray ionization-mass spectrometry (LC/ESI-MS) for HbSSG beta-globin chains. Levels of GSH and thiobarbituric acid substances (TBARS) levels were measured by spectrophotometric and fluorimetric methods, respectively.

RESULTS

The positivity for HbSSG in diabetic subjects with microangiopathy was significantly higher (69%) compared to diabetics without microangiopathy (22%) and control subjects (14%). In univariate regression analysis, HbSSG levels were significantly associated with the duration of diabetes, HbA1c, and TBARS levels. GSH levels were negatively correlated (r = -0.57, P < 0.001) with HbSSG in diabetic subjects. A significant inverse correlation (r = -0.42, P < 0.001) between the GSH levels and HbA1c levels was also seen in diabetic subjects.

CONCLUSIONS

This is perhaps the largest LC-MS-based study to demonstrate that HbSSG levels are markedly increased in diabetic subjects with microangiopathy. Since diabetic subjects also exhibited increased lipid peroxidation and decreased GSH levels, it appears that enhanced oxidative stress may account for the increased HbSSG concentrations and altered reduction-oxidation (redox) signaling.

摘要

目的

蛋白质谷胱甘肽化被认为是复杂疾病发病机制中一种重要的翻译后修饰。本研究的目的是检测糖尿病及其相关微血管病变中，血红蛋白（Hb）是否通过还原型谷胱甘肽（GSH）对存在的巯基进行氧化而被修饰，并确定氧化失衡是否与谷胱甘肽化血红蛋白（HbSSG）水平存在任何关联。

方法

研究组共有130名受试者，包括非糖尿病健康对照者（n = 30）以及患有（n = 53）和未患有（n = 47）微血管病变的2型糖尿病患者。对所有受试者进行血糖和血脂状况评估，而糖尿病患者还需评估视网膜病变和肾病的诊断情况。通过液相色谱/电喷雾电离质谱（LC/ESI-MS）分析所有受试者的红细胞裂解物中的HbSSGβ-珠蛋白链。分别采用分光光度法和荧光法测量GSH水平和硫代巴比妥酸物质（TBARS）水平。

结果

患有微血管病变的糖尿病患者中HbSSG的阳性率（69%）显著高于无微血管病变的糖尿病患者（22%）和对照者（14%）。在单因素回归分析中，HbSSG水平与糖尿病病程、糖化血红蛋白（HbA1c）以及TBARS水平显著相关。糖尿病患者中GSH水平与HbSSG呈负相关（r = -0.57，P < 0.001）。糖尿病患者中GSH水平与HbA1c水平之间也存在显著的负相关（r = -0.42，P < 0.001）。