Effect of tauroursodeoxycholic acid on endoplasmic reticulum stress-induced caspase-12 activation

• DOI: 10.1053/jhep.2002.35441
• Publication Date: 2004-03-08T19:13:12Z
• Authors: Qing Xie; Vladimir I. Khaou...; Charles C. Chung; Joohyun Sohn; Bhuvaneswari Kris...; Dorothy E. Lewis; Boris Yoffe
• Keywords: Tauroursodeoxycholic acid

Activation of death receptors and mitochondrial damage are well-described common apoptotic pathways. Recently, a novel pathway via endoplasmic reticulum (ER) stress has been reported. We assessed the role tauroursodeoxycholic acid (TUDCA) in inhibition caspase-12 activation its effect on calcium homeostasis an ER stress-induced model apoptosis. The human liver-derived cell line, Huh7, was treated with thapsigargin (TG) to induce stress. Typical morphologic changes preceded development changes, including DNA fragmentation cleavage poly (adenosine diphosphate-ribose) polymerase (PARP), as well caspase-3 -7. Elevation intracellular levels without loss membrane potential (MMP) shown using Fluo-3/Fura-red labeling flow cytometry, confirmed by induction Bip/GRP78, calcium-dependent chaperon lumen. These were accompanied procaspase-12 processing. TUDCA abolished TG-induced markers stress; reduced efflux, activation; subsequently inhibited effector caspases In conclusion, we propose that mitochondria play secondary ER-mediated apoptosis prevents blocking calcium-mediated activation. This mechanism action suggests new intervention methods for liver disease.