Watala 2012 Abstract Bioblast

From Bioblast
Watala C, Przygodzki T, Siewiera K, Kassassir H, Talar M, Labieniec-Watala M (2012) Oxygen consumption in resting and activated blood platelets: platelet mitochondria and cyclooxygenases as compounding targets for high-resolution respirometry. Mitochondr Physiol Network 17.12.

Link: MiPNet17.12 Bioblast 2012 - Open Access

Watala C, Przygodzki T, Siewiera K, Kassassir H, Talar M, Labieniec-Watala M (2012)

Event: Bioblast 2012

Cezary Watala

Background and objectives Little is known about the efficiency of mitochondrial respiration in blood platelets under pathological conditions, and it is even more so considering platelets in atherothrombotic states. Under conditions of accelerated arachidonate-prostanoid pathway intraplatelet oxygen is consumed not only by mitochondria, but also by membrane-associated cyclooxygenases [1]. Hence, mitochondria and cyclooxygenases in blood platelets originating from experimentally-diabetic animals constituted two major targets in our studies.

Diabetes impairs platelet prostanoid metabolism, but only slightly affects platelet mitochondria

Diabetic platelets demonstrate enhanced COX-1-mediated eicosanoid metabolism. The increased oxygen consumption in blood platelets from diabetic animals has been attributed to the increased activity of COX-1, while changes in the maximum consumption of oxygen or RCR ratio were very subtle. Interestingly, the activation of platelet COX-1 concerned both cyclooxygenase and peroxidase domain of the enzyme. The pathophysiological implications of such an increased COX-1 activity are very straightforward: elevated synthesis of thrombogenic thromboxane and its contribution to atherothrombosis.

Severe diabetic hyperglycaemia affects platelet COX-1 and endothelial COX-2

The increased COX activity in diabetes may directly result from non-enzymatic modification by sugars and - consequently the advanced changes in protein structure in diabetes. Platelet COX-1 incubated in vitro with excessive glucose or methylglyoxal demonstrated enhanced activity of cyclooxygenase and peroxidase subunits of COX-1, respectively. Such modifications did not abolish the subsequent acetylation of the enzyme (implications for ASA therapy?). Otherwise, COX-2 present in endothelium, demonstrated reduced activity when non-enzymatically modified with glucose, 1,6 bisphosphate fructose or methyl glyoxal.

COX-2-dependent blood vessel vasodilation in diabetes

Dysfunctional, non-enzymatically modified diabetic endothelium demonstrates decreased NO production, but is able to compensate this deficit by enhanced synthesis of COX-2 derived vasodilatory prostaglandins (PGI2 and PGE2). This effect is of special importance when considering the application of selective COX-2 inhibitors known as β€˜coxibs’ in patients with cardiovascular disease.

Non-invasive assay of blood platelet functioning – a new perspective to monitor (patho)physiology of intact circulating platelets

The prevailing majority of experiments on blood platelets reactivity are conducted with the use of in vitro methods. The platelets’ susceptibility to activation upon blood collection, as well as in the course of sample preparation, largely contributes to possible artifactual observations encountered when using these methods. Therefore, validation of methods for in vivo testing on blood platelets reactivity, may become a challenging rationale [2]. In our hands, the agonist-induced platelet aggregation in a bloodstream is monitored in a microcirculation with the use of a non-invasive Laser Doppler Flowmetry.

β€’ Keywords: Blood platelets, Diabetes mellitus, Platelet mitochondria, Glycation, Carbonylation, Cyclooxygenases, COX-1, COX-2, Nitric oxide Prostaglandins, Arachidonate oxidation

β€’ O2k-Network Lab: PL Lodz Watala C

Labels: MiParea: Respiration, mt-Medicine  Pathology: Aging;senescence, Diabetes  Stress:Ischemia-reperfusion, Mitochondrial disease  Organism: Human, Rat  Tissue;cell: Endothelial;epithelial;mesothelial cell, Blood cells, Platelet  Preparation: Intact cells, Isolated mitochondria, Enzyme  Enzyme: Marker enzyme  Regulation: Fatty acid  Coupling state: ROUTINE, ET  Pathway: NS, ROX  HRR: Oxygraph-2k, TIP2k 

Affiliations and author contributions

Cezary Watala (1), Tomasz Przygodzki (1), Karolina Siewiera (1), Hassan Kassassir (1), Marcin Talar (1), Magdalena Labieniec-Watala (2)

(1) Department of Haemostasis and Haemostatic Disorders, Medical University of Lodz, University Clinical Hospital, Lodz, Poland; Email: [email protected]

(2) University of Lodz, Faculty of Biology and Environmental Protection, Department of Thermobiology, Lodz, Poland; Email: [email protected]


  1. Barile ChJ, Herrmann PC, Tyvoll DA, Collman JP, Decreau RA, Bull BS (2012) Inhibiting platelet-stimulated blood coagulation by inhibition of mitochondrial respiration. PNAS 109: 2539–2543. Open Access
  2. Paul W, Queen LR, Page CP, Ferro A (2007) Increased platelet aggregation in vivo in the Zucker Diabetic Fatty rat: differences from the streptozotocin diabetic rat. Br J Pharmacol 150: 105–111. Open Access


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