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Thrombin Induced Apoptosis through Calcium-Mediated Activation of Cytosolic Phospholipase A2 in Intestinal Myofibroblasts

  • Mi Ja, Park (Department of Environmental & Health Chemistry, College of Pharmacy, Chung-Ang University) ;
  • Jong Hoon, Won (Department of Environmental & Health Chemistry, College of Pharmacy, Chung-Ang University) ;
  • Dae Kyong, Kim (Department of Environmental & Health Chemistry, College of Pharmacy, Chung-Ang University)
  • Received : 2022.05.25
  • Accepted : 2022.07.06
  • Published : 2023.01.01

Abstract

Thrombin is a serine protease that participates in a variety of biological signaling through protease-activated receptors. Intestinal myofibroblasts play central roles in maintaining intestinal homeostasis. In this study, we found that thrombin-induced apoptosis is mediated by the calcium-mediated activation of cytosolic phospholipase A2 in the CCD-18Co cell. Thrombin reduced cell viability by inducing apoptosis and proteinase-activated receptor-1 antagonist attenuated thrombin-induced cell death. Endogenous ceramide did not affect the cell viability itself, but a ceramide-mediated pathway was involved in thrombin-induced cell death. Thrombin increased intracellular calcium levels and cytosolic phospholipase A2 activity. The ceramide synthase inhibitor Fumonisin B1, intracellular calcium chelator BAPTA-AM, and cytosolic phospholipase A2 inhibitor AACOCF3 inhibited thrombin-induced cell death. Thrombin stimulated arachidonic acid release and reactive oxygen species generation, which was blocked by AACOCF3, BAPTA-AM, and the antioxidant reagent Trolox. Taken together, thrombin triggered apoptosis through calcium-mediated activation of cytosolic phospholipase A2 in intestinal myofibroblasts.

Keywords

Acknowledgement

This study was supported by grants from the National Research Foundation of Korea (NRF-2017M3A9D8048414) funded by the Korean government (Ministry of Science and ICT).

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