Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Biochem Biophys Res Commun. 2011 Aug 5;411(3):574-9. doi: 10.1016/j.bbrc.2011.06.188. Epub 2011 Jul 13.
Oxidative damage to proteins is one of the major pathogenic mechanisms in many chronic diseases. Therefore, inhibition of this oxidative damage can be an important part of therapeutic strategies. Pyridoxamine (PM), a prospective drug for treatment of diabetic nephropathy, has been previously shown to inhibit several oxidative and glycoxidative pathways, thus protecting amino acid side chains of the proteins from oxidative damage. Here, we demonstrated that PM can also protect protein backbone from fragmentation induced via different oxidative mechanisms including autoxidation of glucose. This protection was due to hydroxyl radical scavenging by PM and may contribute to PM therapeutic effects shown in clinical trials.
蛋白质氧化损伤是许多慢性疾病的主要发病机制之一。因此,抑制这种氧化损伤可以成为治疗策略的重要组成部分。吡哆胺(PM)是一种治疗糖尿病肾病的有前途的药物,先前已显示其可抑制几种氧化和糖基化途径,从而保护蛋白质的氨基酸侧链免受氧化损伤。在这里,我们证明 PM 还可以保护蛋白质主链免受不同氧化机制诱导的碎片化,包括葡萄糖的自动氧化。这种保护归因于 PM 清除羟自由基,并且可能有助于临床试验中 PM 的治疗效果。