The roles of ATP and calcium in morphological changes and cytotoxicity induced by 1,4-benzoquinone in platelets.
To understand the mechanism of 1,4-benzoquinone-induced cytotoxicity in platelets, the roles of ATP and calcium in platelet toxicity and morphological changes were investigated. Using scanning electron microscopy, morphological changes including membrane blebbing were observed in rat platelets 5 min after exposure to 1,4-benzoquinone, which were significantly different from shape changes (pseudopod formation) observed in response to physiological agonists. Benzoquinone-induced membrane blebbing of platelets was associated with rapid depletion of intracellular ATP and was independent of the presence of extracellular calcium. Benzoquinone-induced platelet lysis observed between 20 and 30 min was dependent on extracellular calcium and associated with increased cytosolic calcium. Cytotoxicity induced by 1,4-benzoquinone was inhibited by antagonists of calmodulin, suggesting that calmodulin could play an important role in platelet toxicity. These results suggested that the progression of events for benzoquinone-induced cytotoxicity in platelets was as follows: 1,4-benzoquinone depletes intracellular ATP; membrane blebbing occurs; calcium homeostasis is disrupted, activation of calmodulin-dependent processes results; finally cytotoxicity occurs.
Lee
Sun-Ku
SK
College of Pharmacy, Seoul National University, Shinrim-dong, Seoul 151-742, South Korea.
Chung
Seung-Min
SM
Lee
Moo-Yoel
MY
Lee
Joo-Young
JY
Bae
Ok-Nam
ON
Chung
Jin-Ho
JH
D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D016227:Benzoquinones; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D048429:Cell Size / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D005260:Female; D007770:L-Lactate Dehydrogenase / Q000032:analysis / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D009391:Nephelometry and Turbidimetry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D016227:Benzoquinones; C004532:quinone; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D002118:Calcium