Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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[Ca2+]-dependent Generation of Intracellular Reactive Oxygen Species Mediates Maitotoxin-induced Cellular Responses in Human Umbilical Vein Endothelial Cells

  • Yi, Sun-Ju (Department of Molecular and Cellular Biochemistry, Kangwon National University College of Medicine) ;
  • Kim, Kyung Hwan (Department of Molecular and Cellular Biochemistry, Kangwon National University College of Medicine) ;
  • Choi, Hyun Jung (Department of Molecular and Cellular Biochemistry, Kangwon National University College of Medicine) ;
  • Yoo, Je Ok (Department of Molecular and Cellular Biochemistry, Kangwon National University College of Medicine) ;
  • Jung, Hyo-Il (School of Mechanical Engineering, Yonsei University) ;
  • Han, Jeong-A (Department of Molecular and Cellular Biochemistry, Kangwon National University College of Medicine) ;
  • Kim, Young-Myeong (Department of Molecular and Cellular Biochemistry, Kangwon National University College of Medicine) ;
  • Suh, In Bum (Department of Laboratory Medicine, Kangwon National University College of Medicine) ;
  • Ha, Kwon-Soo (Department of Molecular and Cellular Biochemistry, Kangwon National University College of Medicine)
  • Received : 2005.09.20
  • Accepted : 2005.10.24
  • Published : 2006.02.28
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Abstract

Maitotoxin (MTX) is known as one of the most potent marine toxins involved in Ciguatera poisoning, but intracellular signaling pathways caused by MTX was not fully understood. Thus, we have investigated whether intracellular reactive oxygen species (ROS) are involved in MTX-induced cellular responses in human umbilical vein endothelial cells. MTX induced a dose-dependent increase of intracellular [$Ca^{2+}$]. MTX stimulated the production of intracellular ROS in a dose- and time-dependent manner, which was suppressed by BAPTA-AM, an intracellular $Ca^{2+}$ chelator. Ionomycin also elevated the ROS production in a dose-dependent manner. MTX elevated transamidation activity in a time-dependent manner and the activation was largely inhibited by transfection of tissue transglutaminase siRNA. The activation of tissue transglutaminase and ERK1/2 by MTX was suppressed by BAPTA-AM or ROS scavengers. In addition, MTX-induced cell death was significantly delayed by BAPTA-AM or a ROS scavenger. These results suggest that [$Ca^{2+}$]-dependent generation of intracellular ROS, at least in part, play an important role in MTX-stimulated cellular responses, such as activation of tTGase, ERK phosphorylation, and induction of cell death, in human umbilical vein endothelial cells.

Keywords

Acknowledgement

Supported by : Korea Science and Engineering Foundation

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