Hipkiss A R, Chana H
Molecular Biology and Biophysics Group, King's College London, United Kingdom.
Biochem Biophys Res Commun. 1998 Jul 9;248(1):28-32. doi: 10.1006/bbrc.1998.8806.
Methylglyoxal (MG) (pyruvaldehyde) is an endogenous metabolite which is present in increased concentrations in diabetics and implicated in formation of advanced glycosylation end-products (AGEs) and secondary diabetic complications. Carnosine (beta-alanyl-L-histidine) is normally present in long-lived tissues at concentrations up to 20 mM in humans. Previous studies showed that carnosine can protect proteins against aldehyde-containing cross-linking agents such as aldose and ketose hexose and triose sugars, and malon-dialdehyde, the lipid peroxidation product. Here we examine whether carnosine can protect protein exposed to MG. Our results show that carnosine readily reacts with MG thereby inhibiting MG-mediated protein modification as revealed electrophoretically. We also investigated whether carnosine could intervene when proteins were exposed to an MG-induced AGE (i.e. lysine incubated with MG). Our results show that carnosine can inhibit protein modification induced by a lysine-MG-AGE; this suggests a second intervention site for carnosine and emphasizes its potential as a possible non-toxic modulator of diabetic complications.
甲基乙二醛（MG）（丙酮醛）是一种内源性代谢产物，在糖尿病患者体内浓度升高，与晚期糖基化终产物（AGEs）的形成及继发性糖尿病并发症有关。肌肽（β-丙氨酰-L-组氨酸）在人类长寿组织中的正常浓度高达20 mM。先前的研究表明，肌肽可以保护蛋白质免受含醛交联剂（如醛糖、酮糖己糖和丙糖以及脂质过氧化产物丙二醛）的影响。在此，我们研究肌肽是否能保护暴露于MG的蛋白质。我们的结果表明，肌肽能与MG迅速反应，从而抑制MG介导的蛋白质修饰，这在电泳中得到了证实。我们还研究了在蛋白质暴露于MG诱导的AGE时（即赖氨酸与MG孵育）肌肽是否能起到干预作用。我们的结果表明，肌肽可以抑制赖氨酸-MG-AGE诱导的蛋白质修饰；这表明肌肽存在第二个干预位点，并强调了其作为糖尿病并发症潜在无毒调节剂的可能性。
