- 作者: Yu-Jen Chen; Shoei-Yn; Lin-Shiau
- 作者服務機構: Institutes of Toxicology and Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan
- 中文摘要: --
- 英文摘要: Thapsigargin (TG), an endoplasmic reticular (ER) Ca -ATPase inhibitor, can increase the intracellular calciumconcentration and then deplete the TG-sensitive intracel-lular Ca pool. In this study, we investigated the effectsof TG on cell viability and tumor necrosis factor-α(TNF-α)production in the murine macrophage RAW 264.7 cellline. We found that treatment with TG (10-800 nM)induced apoptosis in RAW 264.7 cells in a dose-depen-dent manner (IC , 200 nM). Lipopolysaccharide (LPS,1 μg/mI) markedly potentiated low concentrations of TG(10-75 nM) in inducing apoptosis (IC , 20 nM) asrevealed by the DNA ladder. Polymycin B (an LPS recep-tor antagonist) inhibited the cytotoxic effect induced byLPS plus TG. Although TG, A23187 and ionomycin alldefinitely increased intracellular Ca concentrations,neither A23187 nor ionomycin mimicked TG in inducingapoptotic events in LPS-activated RAW 264.7 cells. More-over, the production of TNF-α induced by LPS was pro-foundly potentiated by TG but not by A23187 or by iono-mycin. We conclude from these combined results thatTG-sensitive ER Ca stores play a pivotal role in modu-lating cell viability and TNF-a production. The mutualpotentiation between the LIPS receptor signaling path-way and the depletion of ER Ca stores implies the exis-tence of cross-talk between these multiregulatory mech-anisms in this murine macrophage RAW 264.7 cell line.
- 中文關鍵字: --
- 英文關鍵字: --