title: Platelet mitochondrial dysfunction is evident in type 2 diabetes in association with modifications of mitochondrial anti-oxidant stress proteins.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Center for Molecular Medicine, NHLBI, NIH, Bethesda, MD, USA.
authors.forename: C
authors.initials: C
authors.lastname: Avila
authors.forename: R J
authors.initials: RJ
authors.lastname: Huang
authors.forename: M V
authors.initials: MV
authors.lastname: Stevens
authors.forename: A M
authors.initials: AM
authors.lastname: Aponte
authors.forename: D
authors.initials: D
authors.lastname: Tripodi
authors.forename: K Y
authors.initials: KY
authors.lastname: Kim
authors.forename: M N
authors.initials: MN
authors.lastname: Sack
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D016022:Case-Control Studies; D019069:Cell Respiration / Q000187:drug effects / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006360:Heat-Shock Proteins / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000032:analysis / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D010865:Pilot Projects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D040901:Proteomics / Q000379:methods
chemical_list: D000975:Antioxidants; D006360:Heat-Shock Proteins; D024101:Mitochondrial Proteins