Antioxidant defenses in TNF-treated MCF-7 cells

Selective increase in MnSOD

Linda M. Siemankowski, Jeanne Morreale, Margaret M Briehl

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Oxidative stress has been implicated in the mechanism of tumor necrosis factor-α (TNF)-induced apoptosis, raising a question about the status of antioxidant defenses in TNF-sensitive cells. Antioxidant defenses were examined in MCF-7 cells after treatment with TNF. Cell morphology and DNA fragmentation assays were used to confirm increased apoptosis as a result of TNF treatment. The expression and activity of antioxidant defenses were assessed using Northern blot hybridization analyses and biochemical assays, respectively. Five- and ten-fold increases in manganese superoxide dismutase (MnSOD) mRNA were measured after one and five days of TNF treatment, respectively. The expression of copper, zinc superoxide dismutase, catalase or thioredoxin was not altered. An approximate five-fold increase in MnSOD activity followed the change in gene expression, but no difference in the activity of catalase or glutathione peroxidase was seen. Thus, increased MnSOD activity was not accompanied by an increase in other antioxidant defenses and in particular, H2O2-scavenging enzymes. MnSOD has previously been shown to afford protection against TNF-mediated cytotoxicity. The observed lack of increased peroxidase activity is consistent with mitochondrially-generated superoxide anion radical contributing to the mechanism of TNF-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)919-924
Number of pages6
JournalFree Radical Biology and Medicine
Volume26
Issue number7-8
DOIs
StatePublished - Apr 1999

Fingerprint

MCF-7 Cells
Superoxide Dismutase
Tumor Necrosis Factor-alpha
Antioxidants
Apoptosis
Superoxides
Catalase
Assays
Thioredoxins
Oxidative stress
Scavenging
DNA Fragmentation
Cytotoxicity
Glutathione Peroxidase
Gene expression
Northern Blotting
Peroxidase
Zinc
Copper
Oxidative Stress

Keywords

  • Antioxidant defenses
  • Apoptosis
  • Enzyme activity
  • Free radical
  • Gene expression
  • MCF-7 cells
  • Oxidative stress
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Antioxidant defenses in TNF-treated MCF-7 cells : Selective increase in MnSOD. / Siemankowski, Linda M.; Morreale, Jeanne; Briehl, Margaret M.

In: Free Radical Biology and Medicine, Vol. 26, No. 7-8, 04.1999, p. 919-924.

Research output: Contribution to journalArticle

Siemankowski, Linda M. ; Morreale, Jeanne ; Briehl, Margaret M. / Antioxidant defenses in TNF-treated MCF-7 cells : Selective increase in MnSOD. In: Free Radical Biology and Medicine. 1999 ; Vol. 26, No. 7-8. pp. 919-924.
@article{4f31e07a02b64b0991aaa38ed2bfbf48,
title = "Antioxidant defenses in TNF-treated MCF-7 cells: Selective increase in MnSOD",
abstract = "Oxidative stress has been implicated in the mechanism of tumor necrosis factor-α (TNF)-induced apoptosis, raising a question about the status of antioxidant defenses in TNF-sensitive cells. Antioxidant defenses were examined in MCF-7 cells after treatment with TNF. Cell morphology and DNA fragmentation assays were used to confirm increased apoptosis as a result of TNF treatment. The expression and activity of antioxidant defenses were assessed using Northern blot hybridization analyses and biochemical assays, respectively. Five- and ten-fold increases in manganese superoxide dismutase (MnSOD) mRNA were measured after one and five days of TNF treatment, respectively. The expression of copper, zinc superoxide dismutase, catalase or thioredoxin was not altered. An approximate five-fold increase in MnSOD activity followed the change in gene expression, but no difference in the activity of catalase or glutathione peroxidase was seen. Thus, increased MnSOD activity was not accompanied by an increase in other antioxidant defenses and in particular, H2O2-scavenging enzymes. MnSOD has previously been shown to afford protection against TNF-mediated cytotoxicity. The observed lack of increased peroxidase activity is consistent with mitochondrially-generated superoxide anion radical contributing to the mechanism of TNF-induced apoptosis.",
keywords = "Antioxidant defenses, Apoptosis, Enzyme activity, Free radical, Gene expression, MCF-7 cells, Oxidative stress, Tumor necrosis factor-α",
author = "Siemankowski, {Linda M.} and Jeanne Morreale and Briehl, {Margaret M}",
year = "1999",
month = "4",
doi = "10.1016/S0891-5849(98)00273-1",
language = "English (US)",
volume = "26",
pages = "919--924",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",
number = "7-8",

}

TY - JOUR

T1 - Antioxidant defenses in TNF-treated MCF-7 cells

T2 - Selective increase in MnSOD

AU - Siemankowski, Linda M.

AU - Morreale, Jeanne

AU - Briehl, Margaret M

PY - 1999/4

Y1 - 1999/4

N2 - Oxidative stress has been implicated in the mechanism of tumor necrosis factor-α (TNF)-induced apoptosis, raising a question about the status of antioxidant defenses in TNF-sensitive cells. Antioxidant defenses were examined in MCF-7 cells after treatment with TNF. Cell morphology and DNA fragmentation assays were used to confirm increased apoptosis as a result of TNF treatment. The expression and activity of antioxidant defenses were assessed using Northern blot hybridization analyses and biochemical assays, respectively. Five- and ten-fold increases in manganese superoxide dismutase (MnSOD) mRNA were measured after one and five days of TNF treatment, respectively. The expression of copper, zinc superoxide dismutase, catalase or thioredoxin was not altered. An approximate five-fold increase in MnSOD activity followed the change in gene expression, but no difference in the activity of catalase or glutathione peroxidase was seen. Thus, increased MnSOD activity was not accompanied by an increase in other antioxidant defenses and in particular, H2O2-scavenging enzymes. MnSOD has previously been shown to afford protection against TNF-mediated cytotoxicity. The observed lack of increased peroxidase activity is consistent with mitochondrially-generated superoxide anion radical contributing to the mechanism of TNF-induced apoptosis.

AB - Oxidative stress has been implicated in the mechanism of tumor necrosis factor-α (TNF)-induced apoptosis, raising a question about the status of antioxidant defenses in TNF-sensitive cells. Antioxidant defenses were examined in MCF-7 cells after treatment with TNF. Cell morphology and DNA fragmentation assays were used to confirm increased apoptosis as a result of TNF treatment. The expression and activity of antioxidant defenses were assessed using Northern blot hybridization analyses and biochemical assays, respectively. Five- and ten-fold increases in manganese superoxide dismutase (MnSOD) mRNA were measured after one and five days of TNF treatment, respectively. The expression of copper, zinc superoxide dismutase, catalase or thioredoxin was not altered. An approximate five-fold increase in MnSOD activity followed the change in gene expression, but no difference in the activity of catalase or glutathione peroxidase was seen. Thus, increased MnSOD activity was not accompanied by an increase in other antioxidant defenses and in particular, H2O2-scavenging enzymes. MnSOD has previously been shown to afford protection against TNF-mediated cytotoxicity. The observed lack of increased peroxidase activity is consistent with mitochondrially-generated superoxide anion radical contributing to the mechanism of TNF-induced apoptosis.

KW - Antioxidant defenses

KW - Apoptosis

KW - Enzyme activity

KW - Free radical

KW - Gene expression

KW - MCF-7 cells

KW - Oxidative stress

KW - Tumor necrosis factor-α

UR - http://www.scopus.com/inward/record.url?scp=0032925195&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032925195&partnerID=8YFLogxK

U2 - 10.1016/S0891-5849(98)00273-1

DO - 10.1016/S0891-5849(98)00273-1

M3 - Article

VL - 26

SP - 919

EP - 924

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

IS - 7-8

ER -