Platelet Mitochondrial Dysfunction is Evident in Type 2 Diabetes in Association with Modifications of Mitochondrial Anti-Oxidant Stress Proteins

被引：87

作者：

Avila, C. ^{[1
]}

Huang, R. J. ^{[1
]}

Stevens, M. V. ^{[1
]}

Aponte, A. M. ^{[2
]}

Tripodi, D. ^{[1
]}

Kim, K. Y. ^{[1
]}

Sack, M. N. ^{[1
]}

机构：

[1] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA

[2] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA

来源：

EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES | 2012年 / 120卷 / 04期

关键词：

mitochondria; platelets; reactive oxygen species; respiration; diabetes; SKELETAL-MUSCLE; INSULIN-RESISTANCE;

D O I：

10.1055/s-0031-1285833

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 mitochondria( 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.

引用

页码：248 / 251

页数：4

共 15 条

[1]

Baalbaki Hisham A, 2007, Endocr Pract, V13, P679

[2] Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice [J].