没有交叉链接的高级糖化终产品会影响亲激素加工.
Sebastian Brings1,2, Walter Mier2, Barbro Beijer2
1Department of Endocrinology, Metabolism and Clinical Chemistry, University Hospital Heidelberg, Heidelberg, Germany.
The Biochemical journal
|December 19, 2023
概括
先进的糖化终产物 (AGEs) 损害蛋白酶活性,阻碍了诸如益胰岛素之类的必需益激素的转化为活性激素. 这种AGE修饰可能代表了糖尿病和肥胖病原发生的新机制.
科学领域:
- 生物化学 生物化学
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
背景情况:
- 先进的糖化终产品 (AGEs) 是通过氨基酸的非酶性修饰而形成的.
- AGEs与糖尿病并发症有关,可能是由于蛋白质加工受损.
- AGEs对促激素转化为活性激素的影响需要进一步研究.
研究的目的:
- 调查基质的AGE修饰是否会影响蛋白酶对基质的处理.
- 为了确定AGE对亲胰岛素转化为胰岛素的影响.
主要方法:
- 固相合成被用于制造AGE修饰和未修饰的蛋白质酶基质.
- 使用这些合成基质来量化蛋白酶活性.
- 评估了甲基醇修饰的益胰岛素对胰岛素形成的影响.
主要成果:
- AGE修饰 (CML,MG-H1) 显著抑制了蛋白酶活性,囊类甲素显示~50%的减少.
- 素,PCSK和CPE等关键蛋白酶对AGE修饰基质完全无活性.
- 甲基醇修饰的益胰岛素以度依赖的方式将转化为胰岛素减少了高达80%.
结论:
- 用AGE对基质的修改抑制了蛋白酶的活性.
- 基本的前激素加工酶 (PCSK,CPE) 对AGE修饰基质的不活性表明糖尿病和肥胖症的新病理机制.
- AGE修饰对激素处理的影响是代谢疾病病因学的关键因素.
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