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姜黄素通过抑制蛋白质泛素化改善1型糖尿病小鼠的骨骼肌萎缩。

Curcumin ameliorates skeletal muscle atrophy in type 1 diabetic mice by inhibiting protein ubiquitination.

作者信息

Ono Taisuke, Takada Shingo, Kinugawa Shintaro, Tsutsui Hiroyuki

机构信息

Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

出版信息

Exp Physiol. 2015 Sep;100(9):1052-63. doi: 10.1113/EP085049. Epub 2015 Aug 14.

Abstract

What is the central question of this study? We sought to examine whether curcumin could ameliorate skeletal muscle atrophy in diabetic mice by inhibiting protein ubiquitination, inflammatory cytokines and oxidative stress. What is the main finding and its importance? We found that curcumin ameliorated skeletal muscle atrophy in streptozotocin-induced diabetic mice by inhibiting protein ubiquitination without affecting protein synthesis. This favourable effect of curcumin was possibly due to the inhibition of inflammatory cytokines and oxidative stress. Curcumin may be beneficial for the treatment of muscle atrophy in type 1 diabetes mellitus. Skeletal muscle atrophy develops in patients with diabetes mellitus (DM), especially in type 1 DM, which is associated with chronic inflammation. Curcumin, the active ingredient of turmeric, has various biological actions, including anti-inflammatory and antioxidant properties. We hypothesized that curcumin could ameliorate skeletal muscle atrophy in mice with streptozotocin-induced type 1 DM. C57BL/6 J mice were injected with streptozotocin (200 mg kg(-1) i.p.; DM group) or vehicle (control group). Each group of mice was randomly subdivided into two groups of 10 mice each and fed a diet with or without curcumin (1500 mg kg(-1) day(-1)) for 2 weeks. There were significant decreases in body weight, skeletal muscle weight and cellular cross-sectional area of the skeletal muscle in DM mice compared with control mice, and these changes were significantly attenuated in DM+Curcumin mice without affecting plasma glucose and insulin concentrations. Ubiquitination of protein was increased in skeletal muscle from DM mice and decreased in DM+Curcumin mice. Gene expressions of muscle-specific ubiquitin E3 ligase atrogin-1/MAFbx and MuRF1 were increased in DM and inhibited in DM+Curcumin mice. Moreover, nuclear factor-κB activation, concentrations of the inflammatory cytokines tumour necrosis factor-α and interleukin-1β and oxidative stress were increased in the skeletal muscle from DM mice and inhibited in DM+Curcumin mice. Curcumin ameliorated skeletal muscle atrophy in DM mice by inhibiting protein ubiquitination, inflammatory cytokines and oxidative stress. Curcumin may be beneficial for the treatment of muscle atrophy in type 1 DM.

摘要

本研究的核心问题是什么?我们试图研究姜黄素是否能通过抑制蛋白质泛素化、炎性细胞因子和氧化应激来改善糖尿病小鼠的骨骼肌萎缩。主要发现及其重要性是什么?我们发现姜黄素通过抑制蛋白质泛素化改善链脲佐菌素诱导的糖尿病小鼠的骨骼肌萎缩,而不影响蛋白质合成。姜黄素的这种有益作用可能归因于对炎性细胞因子和氧化应激的抑制。姜黄素可能对1型糖尿病患者肌肉萎缩的治疗有益。糖尿病(DM)患者,尤其是1型糖尿病患者会出现骨骼肌萎缩,这与慢性炎症有关。姜黄素是姜黄的活性成分,具有多种生物学作用,包括抗炎和抗氧化特性。我们假设姜黄素可以改善链脲佐菌素诱导的1型糖尿病小鼠的骨骼肌萎缩。将C57BL/6 J小鼠注射链脲佐菌素(200 mg kg(-1)腹腔注射;糖尿病组)或溶剂(对照组)。每组小鼠随机再分为两组,每组10只,分别给予含或不含姜黄素(1500 mg kg(-1)天(-1))的饮食,持续2周。与对照小鼠相比,糖尿病小鼠的体重、骨骼肌重量和骨骼肌细胞横截面积显著降低,而在糖尿病+姜黄素组小鼠中这些变化显著减轻,且不影响血浆葡萄糖和胰岛素浓度。糖尿病小鼠骨骼肌中蛋白质的泛素化增加,而糖尿病+姜黄素组小鼠中则减少。糖尿病组肌肉特异性泛素E3连接酶atrogin-1/MAFbx和MuRF1的基因表达增加,而糖尿病+姜黄素组小鼠中受到抑制。此外,糖尿病小鼠骨骼肌中核因子-κB激活、炎性细胞因子肿瘤坏死因子-α和白细胞介素-1β的浓度以及氧化应激增加,而糖尿病+姜黄素组小鼠中受到抑制。姜黄素通过抑制蛋白质泛素化、炎性细胞因子和氧化应激改善糖尿病小鼠的骨骼肌萎缩。姜黄素可能对1型糖尿病患者肌肉萎缩的治疗有益。

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