Carbon monoxide promotes Fas/CD95-induced apoptosis in Jurkat cells. Academic Article uri icon

Overview

MeSH

  • Adenoviridae
  • Annexin A5
  • Blotting, Western
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases
  • Cell Death
  • Cell Line, Tumor
  • Down-Regulation
  • Enzyme Inhibitors
  • Flow Cytometry
  • HSP70 Heat-Shock Proteins
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Jurkat Cells
  • MAP Kinase Signaling System
  • Propidium
  • Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA
  • RNA, Small Interfering
  • Time Factors
  • Transfection
  • Up-Regulation

MeSH Major

  • Antigens, CD95
  • Apoptosis
  • Carbon Monoxide

abstract

  • A properly functioning immune system is dependent on programmed cell death/apoptosis at virtually every stage of lymphocyte development and activity. Carbon monoxide (CO), an enzymatic product of heme oxyenase-1, has been shown to possess anti-apoptotic effects in a number of different model systems. The purpose of the present study was to expand on this knowledge to determine the role of CO in the well established model of Fas/CD95-induced apoptosis in Jurkat cells, and to determine the mechanism by which CO can modulate T-cell apoptosis. Exposure of Jurkat cells to CO resulted in augmentation in Fas/CD95-induced apoptosis, which correlated with CO-induced up-regulation of the pro-apoptotic protein FADD as well as activation of caspase-8, -9, and -3 while simultaneously down-regulating the anti-apoptotic protein BCL-2. These effects of CO were lost with overexpression of the small interfering RNA of FADD. CO, as demonstrated previously in endothelial cells, was also anti-apoptotic in Jurkat cells against tumor necrosis factor and etoposide. We further demonstrate that this pro-apoptotic effect of CO was independent of reactive oxygen species production and involved inhibition in Fas/CD95-induced activation of the pro-survival ERK MAPK. We conclude that in contrast to other studies showing the anti-apoptotic effects of CO, Fas/CD95-induced cell death in Jurkat cells is augmented by exposure to CO and that this occurs in part via inhibition in the activation of ERK MAPK. These data begin to elucidate specific differences with regard to the effects of CO and cell death pathways and provide important and valuable insight into potential mechanisms of action.

publication date

  • October 22, 2004

has subject area

  • Adenoviridae
  • Annexin A5
  • Antigens, CD95
  • Apoptosis
  • Blotting, Western
  • Carbon Monoxide
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases
  • Cell Death
  • Cell Line, Tumor
  • Down-Regulation
  • Enzyme Inhibitors
  • Flow Cytometry
  • HSP70 Heat-Shock Proteins
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Jurkat Cells
  • MAP Kinase Signaling System
  • Propidium
  • Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA
  • RNA, Small Interfering
  • Time Factors
  • Transfection
  • Up-Regulation

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1074/jbc.M406105200

PubMed ID

  • 15280387

Additional Document Info

start page

  • 44327

end page

  • 44334

volume

  • 279

number

  • 43