Centre for Paediatric and Adolescent Medicine, University Hospital of Heidelberg, 69120 Heidelberg, Germany.
Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, Italy.
Int J Mol Sci. 2018 Sep 13;19(9):2751. doi: 10.3390/ijms19092751.
BACKGROUND/AIMS: In rodents, carnosine treatment improves diabetic nephropathy, whereas little is known about the role and function of anserine, the methylated form of carnosine.
Antioxidant activity was measured by oxygen radical absorbance capacity and oxygen stress response in human renal tubular cells (HK-2) by RT-PCR and Western-Immunoblotting. In wildtype (WT) and diabetic mice (db/db), the effect of short-term anserine treatment on blood glucose, proteinuria and vascular permeability was measured.
Anserine has a higher antioxidant capacity compared to carnosine ( < 0.001). In tubular cells (HK-2) stressed with 25 mM glucose or 20⁻100 µM hydrogen peroxide, anserine but not carnosine, increased intracellular heat shock protein (Hsp70) mRNA and protein levels. In HK-2 cells stressed with glucose, co-incubation with anserine also increased hemeoxygenase (HO-1) protein and reduced total protein carbonylation, but had no effect on cellular sirtuin-1 and thioredoxin protein concentrations. Three intravenous anserine injections every 48 h in 12-week-old db/db mice, improved blood glucose by one fifth, vascular permeability by one third, and halved proteinuria (all < 0.05).
Anserine is a potent antioxidant and activates the intracellular Hsp70/HO-1 defense system under oxidative and glycative stress. Short-term anserine treatment in diabetic mice improves glucose homeostasis and nephropathy.
背景/目的：在啮齿动物中，肌肽治疗可改善糖尿病肾病，而关于肌肽的甲基化形式——鹅肌肽的作用和功能，人们知之甚少。
通过 RT-PCR 和 Western-Immunoblotting 检测人肾小管细胞（HK-2）中的氧自由基吸收能力和氧应激反应，来测量抗氧化活性。在野生型（WT）和糖尿病（db/db）小鼠中，测量短期鹅肌肽治疗对血糖、蛋白尿和血管通透性的影响。
与肌肽相比，鹅肌肽具有更高的抗氧化能力（<0.001）。在 25 mM 葡萄糖或 20-100 µM 过氧化氢应激的肾小管细胞（HK-2）中，鹅肌肽而非肌肽增加了细胞内热休克蛋白（Hsp70）mRNA 和蛋白水平。在葡萄糖应激的 HK-2 细胞中，鹅肌肽的共孵育还增加了血红素加氧酶（HO-1）蛋白并减少了总蛋白羰基化，但对细胞内 Sirtuin-1 和硫氧还蛋白蛋白浓度没有影响。在 12 周龄 db/db 小鼠中，每 48 小时静脉注射 3 次鹅肌肽，可使血糖降低五分之一，血管通透性降低三分之一，蛋白尿减少一半（均<0.05）。
鹅肌肽是一种有效的抗氧化剂，可在氧化和糖化应激下激活细胞内的 Hsp70/HO-1 防御系统。在糖尿病小鼠中短期鹅肌肽治疗可改善葡萄糖稳态和肾病。
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