Methoxetamine Induces Cytotoxicity in H9c2 Cells: Possible Role of p21 Protein (Cdc42/Rac)-Activated Kinase 1

Autor: Kyoung Moon Han, Hye Jin Cha, Jaesuk Yun, Kyung Sik Yoon, Santosh Lamichhane, Soo Kyung Suh, Jisoon Shin, Young-Hoon Kim, Sun Mi Gu
Rok vydání: 2018
Předmět:
Zdroj: Cardiovascular Toxicology. 19:229-236
ISSN: 1559-0259
1530-7905
DOI: 10.1007/s12012-018-9489-4
Popis: The abuse of new psychoactive substances (NPS) is an emerging social problem. Methoxetamine, one of the NPS, was designed as an alternative to ketamine and it was considered an NPS candidate owing to its high addictive potential. However, cardiotoxicity of the phencyclidine analogue, methoxetamine, has not been extensively evaluated. P21 protein (Cdc42/Rac)-activated kinase 1 (PAK-1) is associated with the drug-induced cardiotoxicity and hypertrophy of cardiomyocytes. In the present study, we investigated the effects of methoxetamine on rat cardiomyocytes and PAK-1. Methoxetamine (at 10 µM) reduced cell viability and PAK-1 mRNA levels in H9c2 cells. Methoxetamine treatment (100 µM) decreased the beating rate of primary cardiomyocytes. However, 100 µM methoxetamine-induced heart rate decline was less than 100 µM PCP- or ketamine-induced heart rate decline. Meanwhile, fingolimod hydrochloride (FTY720, 1 µM), a PAK-1 activator, increased cell viability and inhibited hypertrophy induced by methoxetamine in H9c2 cells. These results suggest that methoxetamine may have harmful effects on the cardiovascular system through the regulation of the expression and function of PAK-1.
Databáze: OpenAIRE