Role of Mitochondrial Permeability Transition Pore in Coated-Platelet Formation

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 25; no. 2; pp. 467 - 471
• Main Authors: Remenyi, Gyula, Szasz, Robert, Friese, Paul, Dale, George L
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.02.2005; Hagerstown, MD Lippincott
• Subjects: Adult; Apoptosis; Arsenicals - pharmacology; Atherosclerosis (general aspects, experimental research); Atractyloside - pharmacology; Benzimidazoles - blood; Biological and medical sciences; Blood and lymphatic vessels; Blood coagulation. Blood cells; Blood Platelets - drug effects; Blood Platelets - metabolism; Bongkrekic Acid - pharmacology; Carbocyanines; Cardiology. Vascular system; Collagen - pharmacology; Crotalid Venoms - pharmacology; Cyclosporine - pharmacology; Cytoplasmic Granules - chemistry; Diamide - pharmacology; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Drug Synergism; Flow Cytometry; Fluorescent Dyes - analysis; Fundamental and applied biological sciences. Psychology; Humans; Ion Channels - drug effects; Ion Channels - physiology; Lectins, C-Type; Medical sciences; Membrane Lipids - blood; Mitochondrial Membrane Transport Proteins; Molecular and cellular biology; Phosphatidylserines - blood; Platelet; Platelet Activation - drug effects; Platelet Activation - physiology; Thrombin - pharmacology; Thromboplastin - analysis; Ubiquinone - pharmacology; cyclosporin A; Cardiovascular disease; Oxides; Permeability; coated-platelet; mitochondrial permeability transition pore; Vascular disease; Platelet; phenylarsine oxide; Atherosclerosis; Ciclosporin; Immunosuppressive agent; Phosphatidylserine; coenzyme Q; diamide
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/01.ATV.0000152726.49229.bf

OBJECTIVE—Coated-platelets are a subset of cells observed during costimulation of platelets with collagen and thrombin. Important characteristics of coated-platelets include retention of multiple α-granule proteins and expression of phosphatidylserine on the cell surface. The mitochondrial permeability transition pore (MPTP) is a key step in apoptosis and is suggested to be involved in some forms of platelet activation. The objective of this study was to examine the role of MPTP in the synthesis of coated-platelets. METHODS AND RESULTS—Flow cytometric analysis of coated-platelet production was used to examine the impact of pharmacological effectors of MPTP formation. Cyclosporin A, coenzyme Q, and bongkrekic acid all inhibit MPTP formation as well as production of coated-platelets. Phenylarsine oxide and diamide, both potentiators of MPTP formation, stimulate coated-platelet synthesis. Atractyloside, another inducer of MPTP formation, does not affect the percentage of coated-platelets synthesized; however, it does increase the level of phosphatidylserine exposed on the surface of coated-platelets. CONCLUSIONS—These findings indicate that MPTP formation is an integral event in the synthesis of coated-platelets. Although the exact function of the MPTP remains to be determined, these data support a growing body of evidence that apoptosis-associated events are vital components of the platelet activation process.