Dissociated ROS production and ceramide generation in sulfasalazine-induced cell death in Raw 264.7 cells

B. Salh, K. Assi, S. Huang, L. O'Brien, U. Steinbrecher, A. Gómez-Muñoz

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Sulfasalazine (SSZ) is a drug used in inflammatory bowel disease, whose precise mechanism of action remains to be clarified. Here, we report that incubation of Raw 264.7 cells with SSZ but not salicylates [acetylsalicylic acid (ASA), 4-aminosalicylic acid (4-ASA), and 5-ASA] causes a mixed apoptotic and necrotic form of cell death. In contrast to its metabolites, sulfapyridine and 5-ASA, SSZ exposure in Raw 264.7 cells resulted in a threefold increase in ceramide generation, as well as a robust production of reactive oxygen species (ROS). However, inhibition of ceramide production by fumonisin B1 failed to attenuate cell death. Preincubation with catalase, cyclosporin A (CsA), and bongkrekic acid attenuated ROS production. When dead cells were quantified for apoptotic versus necrotic cell death, catalase and N-acetylcysteine reproducibly attenuated apoptosis, whereas CsA, in addition to reducing apoptosis, was observed to dramatically enhance necrosis. In conclusion, the cell-death response induced by SSZ in Raw 264.7 cells involves ROS in the apoptotic limb but is independent of ceramide formation.

Original languageEnglish (US)
Pages (from-to)790-799
Number of pages10
JournalJournal of Leukocyte Biology
Volume72
Issue number4
StatePublished - Oct 1 2002

Fingerprint

Sulfasalazine
Ceramides
Reactive Oxygen Species
Cell Death
Aspirin
Catalase
Cyclosporine
Bongkrekic Acid
Sulfapyridine
Aminosalicylic Acid
Apoptosis
Salicylates
Acetylcysteine
Inflammatory Bowel Diseases
Necrosis
Extremities
Pharmaceutical Preparations

Keywords

  • Apoptosis
  • Macrophages
  • MAPK
  • Necrosis
  • PLD

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

Cite this

Salh, B., Assi, K., Huang, S., O'Brien, L., Steinbrecher, U., & Gómez-Muñoz, A. (2002). Dissociated ROS production and ceramide generation in sulfasalazine-induced cell death in Raw 264.7 cells. Journal of Leukocyte Biology, 72(4), 790-799.

Dissociated ROS production and ceramide generation in sulfasalazine-induced cell death in Raw 264.7 cells. / Salh, B.; Assi, K.; Huang, S.; O'Brien, L.; Steinbrecher, U.; Gómez-Muñoz, A.

In: Journal of Leukocyte Biology, Vol. 72, No. 4, 01.10.2002, p. 790-799.

Research output: Contribution to journalArticle

Salh, B, Assi, K, Huang, S, O'Brien, L, Steinbrecher, U & Gómez-Muñoz, A 2002, 'Dissociated ROS production and ceramide generation in sulfasalazine-induced cell death in Raw 264.7 cells', Journal of Leukocyte Biology, vol. 72, no. 4, pp. 790-799.
Salh B, Assi K, Huang S, O'Brien L, Steinbrecher U, Gómez-Muñoz A. Dissociated ROS production and ceramide generation in sulfasalazine-induced cell death in Raw 264.7 cells. Journal of Leukocyte Biology. 2002 Oct 1;72(4):790-799.
Salh, B. ; Assi, K. ; Huang, S. ; O'Brien, L. ; Steinbrecher, U. ; Gómez-Muñoz, A. / Dissociated ROS production and ceramide generation in sulfasalazine-induced cell death in Raw 264.7 cells. In: Journal of Leukocyte Biology. 2002 ; Vol. 72, No. 4. pp. 790-799.
@article{900402eb25db4dc8928734c18a952f15,
title = "Dissociated ROS production and ceramide generation in sulfasalazine-induced cell death in Raw 264.7 cells",
abstract = "Sulfasalazine (SSZ) is a drug used in inflammatory bowel disease, whose precise mechanism of action remains to be clarified. Here, we report that incubation of Raw 264.7 cells with SSZ but not salicylates [acetylsalicylic acid (ASA), 4-aminosalicylic acid (4-ASA), and 5-ASA] causes a mixed apoptotic and necrotic form of cell death. In contrast to its metabolites, sulfapyridine and 5-ASA, SSZ exposure in Raw 264.7 cells resulted in a threefold increase in ceramide generation, as well as a robust production of reactive oxygen species (ROS). However, inhibition of ceramide production by fumonisin B1 failed to attenuate cell death. Preincubation with catalase, cyclosporin A (CsA), and bongkrekic acid attenuated ROS production. When dead cells were quantified for apoptotic versus necrotic cell death, catalase and N-acetylcysteine reproducibly attenuated apoptosis, whereas CsA, in addition to reducing apoptosis, was observed to dramatically enhance necrosis. In conclusion, the cell-death response induced by SSZ in Raw 264.7 cells involves ROS in the apoptotic limb but is independent of ceramide formation.",
keywords = "Apoptosis, Macrophages, MAPK, Necrosis, PLD",
author = "B. Salh and K. Assi and S. Huang and L. O'Brien and U. Steinbrecher and A. G{\'o}mez-Mu{\~n}oz",
year = "2002",
month = "10",
day = "1",
language = "English (US)",
volume = "72",
pages = "790--799",
journal = "Journal of Leukocyte Biology",
issn = "0741-5400",
publisher = "FASEB",
number = "4",

}

TY - JOUR

T1 - Dissociated ROS production and ceramide generation in sulfasalazine-induced cell death in Raw 264.7 cells

AU - Salh, B.

AU - Assi, K.

AU - Huang, S.

AU - O'Brien, L.

AU - Steinbrecher, U.

AU - Gómez-Muñoz, A.

PY - 2002/10/1

Y1 - 2002/10/1

N2 - Sulfasalazine (SSZ) is a drug used in inflammatory bowel disease, whose precise mechanism of action remains to be clarified. Here, we report that incubation of Raw 264.7 cells with SSZ but not salicylates [acetylsalicylic acid (ASA), 4-aminosalicylic acid (4-ASA), and 5-ASA] causes a mixed apoptotic and necrotic form of cell death. In contrast to its metabolites, sulfapyridine and 5-ASA, SSZ exposure in Raw 264.7 cells resulted in a threefold increase in ceramide generation, as well as a robust production of reactive oxygen species (ROS). However, inhibition of ceramide production by fumonisin B1 failed to attenuate cell death. Preincubation with catalase, cyclosporin A (CsA), and bongkrekic acid attenuated ROS production. When dead cells were quantified for apoptotic versus necrotic cell death, catalase and N-acetylcysteine reproducibly attenuated apoptosis, whereas CsA, in addition to reducing apoptosis, was observed to dramatically enhance necrosis. In conclusion, the cell-death response induced by SSZ in Raw 264.7 cells involves ROS in the apoptotic limb but is independent of ceramide formation.

AB - Sulfasalazine (SSZ) is a drug used in inflammatory bowel disease, whose precise mechanism of action remains to be clarified. Here, we report that incubation of Raw 264.7 cells with SSZ but not salicylates [acetylsalicylic acid (ASA), 4-aminosalicylic acid (4-ASA), and 5-ASA] causes a mixed apoptotic and necrotic form of cell death. In contrast to its metabolites, sulfapyridine and 5-ASA, SSZ exposure in Raw 264.7 cells resulted in a threefold increase in ceramide generation, as well as a robust production of reactive oxygen species (ROS). However, inhibition of ceramide production by fumonisin B1 failed to attenuate cell death. Preincubation with catalase, cyclosporin A (CsA), and bongkrekic acid attenuated ROS production. When dead cells were quantified for apoptotic versus necrotic cell death, catalase and N-acetylcysteine reproducibly attenuated apoptosis, whereas CsA, in addition to reducing apoptosis, was observed to dramatically enhance necrosis. In conclusion, the cell-death response induced by SSZ in Raw 264.7 cells involves ROS in the apoptotic limb but is independent of ceramide formation.

KW - Apoptosis

KW - Macrophages

KW - MAPK

KW - Necrosis

KW - PLD

UR - http://www.scopus.com/inward/record.url?scp=0036826735&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036826735&partnerID=8YFLogxK

M3 - Article

VL - 72

SP - 790

EP - 799

JO - Journal of Leukocyte Biology

JF - Journal of Leukocyte Biology

SN - 0741-5400

IS - 4

ER -