Heme oxygenase-1 inhibits TNF-α-induced apoptosis in cultured fibroblasts

Irina Petrache, Leo E. Otterbein, Jawed Alam, Gordon W. Wiegand, Augustine M K Choi

Research output: Contribution to journalArticle

251 Citations (Scopus)

Abstract

Heme oxygenase (HO)-1 catalyzes the oxidative cleavage of heme to yield equimolar amounts of biliverdin, iron, and carbon monoxide. HO-1 is a stress response protein, the induction of which is associated with protection against oxidative stress. The mechanism(s) of protection is not completely elucidated, although it is suggested that one or more of the catalytic by- products provide antioxidant functions either directly or indirectly. The involvement of reactive oxygen species in apoptosis raised the question of a possible role for HO-1 in programmed cell death. Using the tetracycline- regulated expression system, we show here that conditional overexpression of HO-1 prevents tumor necrosis factor-α-induced apoptosis in murine L929 fibroblasts. Inhibition of apoptosis was not observed in the presence of tin protoporphyrin, a specific inhibitor of HO activity, and in cells overexpressing antisense HO-1. Interestingly, exogenous administration of a low concentration of carbon monoxide also prevented tumor necrosis factor- α-induced apoptosis in L929 fibroblasts. Inhibition of tumor necrosis factor-α-induced apoptosis by HO-1 overexpression was reversed by 1H- (1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one, an inhibitor of guanylate cyclase, which is a target enzyme for carbon monoxide. Taken together, our data suggest that the antiapoptotic effect of HO-1 may be mediated via carbon monoxide.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume278
Issue number2 22-2
StatePublished - Feb 2000
Externally publishedYes

Fingerprint

Heme Oxygenase-1
Fibroblasts
Apoptosis
Carbon Monoxide
Tumor Necrosis Factor-alpha
Biliverdine
Heme Oxygenase (Decyclizing)
Guanylate Cyclase
Heat-Shock Proteins
Tetracycline
Heme
Reactive Oxygen Species
Oxidative Stress
Cell Death
Iron
Antioxidants
Enzymes

Keywords

  • Carbon monoxide
  • Oxidants
  • Programmed cell death
  • Reactive oxygen species
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Heme oxygenase-1 inhibits TNF-α-induced apoptosis in cultured fibroblasts. / Petrache, Irina; Otterbein, Leo E.; Alam, Jawed; Wiegand, Gordon W.; Choi, Augustine M K.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 278, No. 2 22-2, 02.2000.

Research output: Contribution to journalArticle

Petrache, Irina ; Otterbein, Leo E. ; Alam, Jawed ; Wiegand, Gordon W. ; Choi, Augustine M K. / Heme oxygenase-1 inhibits TNF-α-induced apoptosis in cultured fibroblasts. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2000 ; Vol. 278, No. 2 22-2.
@article{a41d2570923544e98588851e3b5b9c68,
title = "Heme oxygenase-1 inhibits TNF-α-induced apoptosis in cultured fibroblasts",
abstract = "Heme oxygenase (HO)-1 catalyzes the oxidative cleavage of heme to yield equimolar amounts of biliverdin, iron, and carbon monoxide. HO-1 is a stress response protein, the induction of which is associated with protection against oxidative stress. The mechanism(s) of protection is not completely elucidated, although it is suggested that one or more of the catalytic by- products provide antioxidant functions either directly or indirectly. The involvement of reactive oxygen species in apoptosis raised the question of a possible role for HO-1 in programmed cell death. Using the tetracycline- regulated expression system, we show here that conditional overexpression of HO-1 prevents tumor necrosis factor-α-induced apoptosis in murine L929 fibroblasts. Inhibition of apoptosis was not observed in the presence of tin protoporphyrin, a specific inhibitor of HO activity, and in cells overexpressing antisense HO-1. Interestingly, exogenous administration of a low concentration of carbon monoxide also prevented tumor necrosis factor- α-induced apoptosis in L929 fibroblasts. Inhibition of tumor necrosis factor-α-induced apoptosis by HO-1 overexpression was reversed by 1H- (1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one, an inhibitor of guanylate cyclase, which is a target enzyme for carbon monoxide. Taken together, our data suggest that the antiapoptotic effect of HO-1 may be mediated via carbon monoxide.",
keywords = "Carbon monoxide, Oxidants, Programmed cell death, Reactive oxygen species, Tumor necrosis factor-α",
author = "Irina Petrache and Otterbein, {Leo E.} and Jawed Alam and Wiegand, {Gordon W.} and Choi, {Augustine M K}",
year = "2000",
month = "2",
language = "English (US)",
volume = "278",
journal = "American Journal of Physiology",
issn = "0193-1857",
publisher = "American Physiological Society",
number = "2 22-2",

}

TY - JOUR

T1 - Heme oxygenase-1 inhibits TNF-α-induced apoptosis in cultured fibroblasts

AU - Petrache, Irina

AU - Otterbein, Leo E.

AU - Alam, Jawed

AU - Wiegand, Gordon W.

AU - Choi, Augustine M K

PY - 2000/2

Y1 - 2000/2

N2 - Heme oxygenase (HO)-1 catalyzes the oxidative cleavage of heme to yield equimolar amounts of biliverdin, iron, and carbon monoxide. HO-1 is a stress response protein, the induction of which is associated with protection against oxidative stress. The mechanism(s) of protection is not completely elucidated, although it is suggested that one or more of the catalytic by- products provide antioxidant functions either directly or indirectly. The involvement of reactive oxygen species in apoptosis raised the question of a possible role for HO-1 in programmed cell death. Using the tetracycline- regulated expression system, we show here that conditional overexpression of HO-1 prevents tumor necrosis factor-α-induced apoptosis in murine L929 fibroblasts. Inhibition of apoptosis was not observed in the presence of tin protoporphyrin, a specific inhibitor of HO activity, and in cells overexpressing antisense HO-1. Interestingly, exogenous administration of a low concentration of carbon monoxide also prevented tumor necrosis factor- α-induced apoptosis in L929 fibroblasts. Inhibition of tumor necrosis factor-α-induced apoptosis by HO-1 overexpression was reversed by 1H- (1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one, an inhibitor of guanylate cyclase, which is a target enzyme for carbon monoxide. Taken together, our data suggest that the antiapoptotic effect of HO-1 may be mediated via carbon monoxide.

AB - Heme oxygenase (HO)-1 catalyzes the oxidative cleavage of heme to yield equimolar amounts of biliverdin, iron, and carbon monoxide. HO-1 is a stress response protein, the induction of which is associated with protection against oxidative stress. The mechanism(s) of protection is not completely elucidated, although it is suggested that one or more of the catalytic by- products provide antioxidant functions either directly or indirectly. The involvement of reactive oxygen species in apoptosis raised the question of a possible role for HO-1 in programmed cell death. Using the tetracycline- regulated expression system, we show here that conditional overexpression of HO-1 prevents tumor necrosis factor-α-induced apoptosis in murine L929 fibroblasts. Inhibition of apoptosis was not observed in the presence of tin protoporphyrin, a specific inhibitor of HO activity, and in cells overexpressing antisense HO-1. Interestingly, exogenous administration of a low concentration of carbon monoxide also prevented tumor necrosis factor- α-induced apoptosis in L929 fibroblasts. Inhibition of tumor necrosis factor-α-induced apoptosis by HO-1 overexpression was reversed by 1H- (1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one, an inhibitor of guanylate cyclase, which is a target enzyme for carbon monoxide. Taken together, our data suggest that the antiapoptotic effect of HO-1 may be mediated via carbon monoxide.

KW - Carbon monoxide

KW - Oxidants

KW - Programmed cell death

KW - Reactive oxygen species

KW - Tumor necrosis factor-α

UR - http://www.scopus.com/inward/record.url?scp=0034054881&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034054881&partnerID=8YFLogxK

M3 - Article

C2 - 10666115

AN - SCOPUS:0034054881

VL - 278

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0193-1857

IS - 2 22-2

ER -