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Development of a Mammalian Tet-On Expression Cell Line

Glucosylceramide Synthase Regulates TNF-α-Induced Apoptosis
  • Yong-Yu Liu
  • Myles C. Cabot
Part of the Methods in Molecular Biology book series (MIMB, volume 249)

Abstract

Tumor necrosis factor-α (TNF-α) is one of the most pleiotropic of cytokines, acting as a host defense factor in myriad immunological and inflammatory responses and antitumor activity (1, 2, 3). The cytotoxic effects of TNF-α are primarily mediated through TNF-R1 and the receptor-associated proteins, TNF-R1-associated death domain protein (TRADD) and Fas-associated death domain (FADD/MORT1) (3, 4, 5). Ceramide generation and caspase activation represent potential regulation points of apoptotic signaling by TNF-α (6,7). Increased ceramide formation via sphingomyelinase represents an early event in the apoptotic cascade of TNF-α (6,8,9). In MCF-7 breast cancer cells, ceramide is one of the essential molecules in TNF-α-induced apoptosis (10, 11, 12). Increased ceramide generation induced by the P-glycoprotein blocker PSC 833, restores TNF-α-induced apoptosis in KG1a leukemia cells (13), whereas loss of ceramide production is a cause of cellular resistance to apoptosis induced by TNF-α (14). Glucosylceramide synthase (GCS), converting ceramide into glucosylceramide (15), exerts strong influence over cellular ceramide levels and is thus a major modulator of programmed cell death (16). Introducing the GCS gene into TNF-α-sensitive MCF-7 cells greatly diminishes cellular response to TNF-α cytotoxicity (12).

Keywords

Transfection Solution Host Defense Factor Mammalian Transfection Rinse Cell Cellular Ceramide Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Humana Press Inc., Totowa, NJ 2004

Authors and Affiliations

  • Yong-Yu Liu
    • 1
  • Myles C. Cabot
    • 2
  1. 1.John Wayne Cancer Institute at Saint John’s Health CenterSanta MonicaUSA
  2. 2.John Wayne Cancer Institute at Saint John’s Health CenterSanta MonicaUSA

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