UBE2B与分解代谢的C2C12肌管中的肌原纤维蛋白损失有关。
UBE2B is implicated in myofibrillar protein loss in catabolic C2C12 myotubes.
作者信息
Polge Cécile, Leulmi Roza, Jarzaguet Marianne, Claustre Agnes, Combaret Lydie, Béchet Daniel, Heng Anne-Elisabeth, Attaix Didier, Taillandier Daniel
机构信息
INRA, UMR 1019, UNH, CRNH Auvergne Saint Genès Champanelle F-63122 France; Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine BP 10448 Clermont-Ferrand F-63000 France.
INRA, UMR 1019, UNH, CRNH Auvergne Saint Genès Champanelle F-63122 France; Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine BP 10448 Clermont-Ferrand F-63000 France; Service de Néphrologie Réanimation Médicale, Pôle Respiratoire, Endocrinologie-Diabétologie, Urologie, Néphrologie-Dialyse, Nutrition Clinique, Infectiologie, Réanimation Médicale, Hygiène Hospitalière (REUNNIRH) Clermont-Ferrand France.
出版信息
J Cachexia Sarcopenia Muscle. 2016 Jun;7(3):377-87. doi: 10.1002/jcsm.12060. Epub 2015 Nov 19.
BACKGROUND
Skeletal muscle protein loss is an adaptive response to various patho-physiological situations, and the ubiquitin proteasome system (UPS) is responsible for the degradation of the bulk of muscle proteins. The role of E2 ubiquitin-conjugating enzymes is still poorly understood in skeletal muscle.
METHODS
We screened for E2s expression levels in C2C12 myotubes submitted to the catabolic glucocorticoid dexamethasone (Dex).
RESULTS
One micromolar Dex induced an accumulation of proteasome substrates (polyUb conjugates) and an overexpression of the muscle-specific E3 ligase MuRF1 and of six E2 enzymes, UBE2A, UBE2B, UBE2D1, UBE2D2, UBE2G1, and UBE2J1. However, only MuRF1 and UBE2B were sensitive to mild catabolic conditions (0.16 μM Dex). UBE2B knockdown induced a sharp decrease of total (-18%) and K48 (-28%) Ub conjugates, that is, proteasome substrates, indicating an important role of UBE2B in the overall protein breakdown in catabolic myotubes.
CONCLUSIONS
Interestingly, these results indicate an important role of UBE2B on muscle protein homeostasis during catabolic conditions.
背景
骨骼肌蛋白丢失是对各种病理生理状况的一种适应性反应，泛素蛋白酶体系统（UPS）负责大部分肌肉蛋白的降解。E2泛素结合酶在骨骼肌中的作用仍知之甚少。
方法
我们筛选了在分解代谢的糖皮质激素地塞米松（Dex）作用下C2C12肌管中E2s的表达水平。
结果
1微摩尔的Dex诱导蛋白酶体底物（多聚泛素缀合物）积累，以及肌肉特异性E3连接酶MuRF1和六种E2酶UBE2A、UBE2B、UBE2D1、UBE2D2、UBE2G1和UBE2J1的过表达。然而，只有MuRF1和UBE2B对轻度分解代谢条件（0.16μM Dex）敏感。UBE2B基因敲低导致总泛素缀合物（-18%）和K48泛素缀合物（-28%）即蛋白酶体底物急剧减少，表明UBE2B在分解代谢肌管的整体蛋白质分解中起重要作用。
结论
有趣的是，这些结果表明UBE2B在分解代谢条件下对肌肉蛋白稳态起重要作用。
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