RRC ID 52402
著者 Matsunaga T, Morikawa Y, Kamase K, Horinouchi M, Sasajima Y, Suenami K, Sato K, Takekoshi Y, Endo S, El-Kabbani O, Ikari A.
タイトル Enhancement of Endothelial Barrier Permeability by Mitragynine.
ジャーナル Biol Pharm Bull
Abstract Persistent inhalation of mitragynine (MG), a major alkaloid in the leaves of Mitragyna speciosa, causes various systemic adverse effects such as seizure, diarrhea and arthralgias, but its toxicity to endothelial cells and effects on barrier function of the cells are poorly understood. In this study, we compared toxicities of MG and mitraphylline, another constituent of the leaves, against human aortic endothelial (HAE), bronchial BEAS-2B, neuronal SK-N-SH, hepatic HepG2, kidney HEK293, gastric MKN45, colon DLD1, lung A549, breast MCF7 and prostate LNCaP cells, and found that MG, but not mitraphylline, shows higher toxicity to HAE cells compared to the other cells. Forty-eight-hours incubation of HAE cells with a high concentration of MG (60 µM) provoked apoptotic cell death, which was probably due to signaling through enhanced reactive oxygen species (ROS) generation and resultant caspase activation. Treatment of the cells with MG at sublethal concentrations less than 20 µM significantly lowered transendothelial electrical resistance and elevated paracellular permeability, without affecting the cell viability. In addition, the MG-elicited lowering of the resistance was abolished by a ROS inhibitor N-acetyl-L-cysteine and augmented by H2O2 and 9,10-phenanthrenequinone, which generates ROS through its redox cycle. These results suggest the contribution of ROS generation to the increase in endothelial barrier permeability.
巻・号 40(10)
ページ 1779-1783
公開日 2017-1-1
DOI 10.1248/bpb.b17-00117
PMID 28966251
MeSH Apoptosis / drug effects Caspase 3 / metabolism Cell Line Cell Line, Tumor DNA Fragmentation Endothelial Cells / drug effects* Endothelial Cells / metabolism Humans Permeability / drug effects Reactive Oxygen Species / metabolism Secologanin Tryptamine Alkaloids / pharmacology*
IF 1.863
引用数 1
リソース情報
ヒト・動物細胞 SK-N-SH(RCB0426)