Aquilano Katia, Baldelli Sara, La Barbera Livia, Lettieri Barbato Daniele, Tatulli Giuseppe, Ciriolo Maria Rosa
Department of Biology, University of Rome 'Tor Vergata', Rome, Italy.
IRCCS San Raffaele 'La Pisana', Rome, Italy.
Oncotarget. 2016 Apr 26;7(17):23019-32. doi: 10.18632/oncotarget.8552.
During aging skeletal muscle shows an accumulation of oxidative damage as well as intramyocellular lipid droplets (IMLDs). However, although the impact of these modifications on muscle tissue physiology is well established, the direct effectors critical for their occurrence are poorly understood. Here we show that during aging the main lipase of triacylglycerols, ATGL, significantly declines in gastrocnemius and its downregulation in C2C12 myoblast leads to the accumulation of lipid droplets. Indeed, we observed an increase of oxidative damage to proteins in terms of carbonylation, S-nitrosylation and ubiquitination that is dependent on a defective antioxidant cell response mediated by ATGL-PPARα-PGC-1α. Overall our findings describe a pivotal role for ATGL in the antioxidant/anti-inflammatory response of muscle cells highlighting this lipase as a therapeutic target for fighting the progressive decline in skeletal muscle mass and strength.
在衰老过程中，骨骼肌会出现氧化损伤以及肌内脂质滴（IMLDs）的积累。然而，尽管这些修饰对肌肉组织生理学的影响已得到充分证实，但其发生的关键直接效应因子却知之甚少。在这里，我们表明，在衰老过程中，甘油三酯的主要脂肪酶——脂肪甘油三酯脂酶（ATGL）在腓肠肌中显著下降，并且其在C2C12成肌细胞中的下调会导致脂质滴的积累。事实上，我们观察到蛋白质的氧化损伤在羰基化、S-亚硝基化和泛素化方面有所增加，这取决于由ATGL-过氧化物酶体增殖物激活受体α（PPARα）-过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）介导的抗氧化细胞反应缺陷。总体而言，我们的研究结果描述了ATGL在肌肉细胞抗氧化/抗炎反应中的关键作用，突出了这种脂肪酶作为对抗骨骼肌质量和力量逐渐下降的治疗靶点。
