血小板线粒体功能障碍在2型糖尿病中很明显，与线粒体抗氧化应激蛋白的改变有关。
Platelet mitochondrial dysfunction is evident in type 2 diabetes in association with modifications of mitochondrial anti-oxidant stress proteins.
作者信息
Avila C, Huang R J, Stevens M V, Aponte A M, Tripodi D, Kim K Y, Sack M N
机构信息
Center for Molecular Medicine, NHLBI, NIH, Bethesda, MD, USA.
出版信息
Exp Clin Endocrinol Diabetes. 2012 Apr;120(4):248-51. doi: 10.1055/s-0031-1285833. Epub 2011 Sep 15.
OBJECTIVE
Mitochondrial dysfunction and oxidative stress in insulin responsive tissues is implicated in the pathogenesis of type 2 diabetes. Whether these perturbations extend to other tissues and contribute to their pathophysiology is less well established. The objective of this study was to investigate platelet mitochondria to evaluate whether type 2 diabetes associated mitochondrial dysfunction is evident in circulating cells.
METHOD
A pilot study of mitochondrial respiratory function and proteomic changes comparing platelets extracted from insulin sensitive (n=8) and type 2 diabetic subjects (n=7).
RESULTS
In-situ platelet mitochondria show diminished oxygen consumption and lower oxygen-dependent ATP synthesis in diabetic vs. control subjects. Mass spectrometric identification and confirmatory immunoblot analysis identifies induction of the mitochondrial anti-oxidant enzymes superoxide dismutase 2 and thioredoxin-dependent peroxide reductase 3 in platelets of diabetic subjects. As oxidative stress upregulates anti-oxidant enzymes we assessed mitochondrial protein carbonylation as an index of oxidative-stress. Platelets of diabetic subjects exhibit significantly increased protein carbonylation compared to controls.
CONCLUSIONS
As platelets are anuclear fragments of megakaryocytes, our data suggest that the bone marrow compartment in type 2 diabetic subjects is exposed to increased mitochondrial oxidative stress with upregulation of nuclear-encoded antioxidant mitochondrial enzymes. This 'stress-signature' in platelets of diabetic subjects is associated with a diminution of their mitochondrial contribution to energy production and support that mitochondrial perturbations in type 2 diabetes extends beyond the classical insulin responsive tissues. Platelets, as "accessible human tissue", may be useful to measure the mitochondrial modulatory effects of emerging anti-diabetic therapeutics.
目的
胰岛素反应性组织中的线粒体功能障碍和氧化应激与2型糖尿病的发病机制有关。这些紊乱是否扩展到其他组织并导致其病理生理学变化尚不太明确。本研究的目的是研究血小板线粒体，以评估2型糖尿病相关的线粒体功能障碍在循环细胞中是否明显。
方法
一项初步研究，比较从胰岛素敏感者（n = 8）和2型糖尿病患者（n = 7）中提取的血小板的线粒体呼吸功能和蛋白质组学变化。
结果
与对照组相比，糖尿病患者原位血小板线粒体的氧消耗量减少，氧依赖性ATP合成降低。质谱鉴定和验证性免疫印迹分析确定糖尿病患者血小板中线粒体抗氧化酶超氧化物歧化酶2和硫氧还蛋白依赖性过氧化物还原酶3的诱导。由于氧化应激会上调抗氧化酶，我们评估了线粒体蛋白羰基化作为氧化应激的指标。与对照组相比，糖尿病患者的血小板表现出明显增加的蛋白羰基化。
结论
由于血小板是巨核细胞的无核碎片，我们的数据表明，2型糖尿病患者的骨髓区室暴露于增加的线粒体氧化应激中，核编码的抗氧化线粒体酶上调。糖尿病患者血小板中的这种“应激特征”与线粒体对能量产生的贡献减少有关，并支持2型糖尿病中的线粒体紊乱超出了经典的胰岛素反应性组织。血小板作为“可获取的人体组织”，可能有助于测量新型抗糖尿病治疗药物的线粒体调节作用。
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