title: Chlorin e6 Prevents ADP-Induced Platelet Aggregation by Decreasing PI3K-Akt Phosphorylation and Promoting cAMP Production.
abstract: A number of reagents that prevent thrombosis have been developed but were found to have serious side effects. Therefore, we sought to identify complementary and alternative medicinal materials that are safe and have long-term efficacy. In the present studies, we have assessed the ability of chlorine e6 (CE6) to inhibit ADP-induced aggregation of rat platelets and elucidated the underlying mechanism. CE6 inhibited platelet aggregation induced by 10 µM ADP in a concentration-dependent manner and decreased intracellular calcium mobilization and granule secretion (i.e., ATP and serotonin release). Western blotting revealed that CE6 strongly inhibited the phosphorylations of PI3K, Akt, c-Jun N-terminal kinase (JNK), and different mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase 1/2 (ERK1/2) as well as p38-MAPK. Our study also demonstrated that CE6 significantly elevated intracellular cAMP levels and decreased thromboxane A2 formation in a concentration-dependent manner. Furthermore, we determined that CE6 initiated the activation of PKA, an effector of cAMP. Taken together, our findings indicate that CE6 may inhibit ADP-induced platelet activation by elevating cAMP levels and suppressing PI3K/Akt activity. Finally, these results suggest that CE6 could be developed as therapeutic agent that helps prevent thrombosis and ischemia.
authors.affiliation: Laboratory of Veterinary Physiology and Cell Signaling, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Park
authors.forename: Hyun Dong
authors.initials: HD
authors.lastname: Ji
authors.forename: Bo Ra
authors.initials: BR
authors.lastname: Jeon
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Im
authors.forename: Young Min
authors.initials: YM
authors.lastname: Son
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Dong-Ha
authors.initials: DH
authors.lastname: Lee
authors.forename: Young-Chul
authors.initials: YC
authors.lastname: Lee
authors.forename: Eujin
authors.initials: E
authors.lastname: Hyun
authors.forename: Qi
authors.initials: Q
authors.lastname: Jia
authors.forename: Mei
authors.initials: M
authors.lastname: Hong
authors.forename: Hwa-Jin
authors.initials: HJ
authors.lastname: Park
authors.forename: Man Hee
authors.initials: MH
authors.lastname: Rhee