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http://dx.doi.org/10.15616/BSL.2021.27.3.170

Thapsigargin Induces Platelet Aggregation, thereby Releases Lactate Dehydrogenase from Rat Platelets  

Baik, Ji Sue (Research Center, Dongnam Institute of Radiological & Medical Sciences)
Seo, You Na (Research Center, Dongnam Institute of Radiological & Medical Sciences)
Rhee, Man Hee (Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University)
Park, Moon-Taek (Research Center, Dongnam Institute of Radiological & Medical Sciences)
Kim, Sung Dae (Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University)
Publication Information
Biomedical Science Letters / v.27, no.3, 2021 , pp. 170-176 More about this Journal
Abstract
Thapsigargin (TG), a sarco/endoplasmic reticulum (ER) Ca2+-ATPase (SERCA) inhibitor, has been widely used as an agonist for platelet aggregation for decades. In this study, we investigated the effect of TG on the release of lactate dehydrogenase (LDH) for platelets and elucidated its mechanism. Platelet LDH release and platelet aggregation were increased by TG treatment; 1,000 nM of TG induced the complete lysis of platelets. Other agonists such as collagen (2.5 ㎍/mL), thrombin (0.1 U/mL), and ADP (10 mM) did not induce significant platelet LDH release despite platelet aggregation. Finally, we investigated the effects of pharmacological inhibitors on TG-induced platelet aggregation and LDH release. SP600125, a JNK inhibitor, and LY294002, a PI-3K inhibitor, inhibited TG-induced platelet LDH release but not platelet aggregation. Forskolin, an adenylyl cyclase activator, also inhibited LDH release without affecting platelet aggregation by TG. These results suggest that the TG-induced platelet aggregation was accompanied by LDH release but regulated by a different signaling pathway.
Keywords
Platelets; Thapsigargin; Lactate dehydrogenase; cAMP; JNK; PI-3K;
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