Abstract

Heme oxygenase-1 (HO-1) is induced as a beneficial and adaptive response in cells and tissues exposed to oxidative stress. Herein we examined how various eicosanoids affect the induction of HO-1, and the possible mechanism underlying 15-deoxy-Δ12,14- prostaglandin J2 (15d-PGJ2)-induced HO-1 expression. PGH2, PGD2 and its metabolites of the PGJ2 series, and PGA1 markedly induced the protein expression of HO-1. Arachidonic acid (AA), docosahexaenoic acid (DHA), PGE2, PGF, and thromboxane B 2 (TXB2) were shown to have no effect on the induction of HO-1. 15d-PGJ2 was the most potent activator achieving significance at 5 μM. Although 15d-PGJ2 significantly activated the MAPKs of JNK and ERK, the activation of JNK and ERK did not contribute to the induction of HO-1 as determined using transfection of dominant-negative plasmids and MAPKs inhibitors. Additional experiment indicated that 15d-PGJ2 induced HO-1 expression through peroxisome proliferator-activated receptor (PPAR)-independent pathway. 15d-PGJ2 significantly decreased the intracellular level of reduced glutathione; and the thiol antioxidant, N-acetyl-L-cysteine (NAC), and the thiol-reducing agent, dithiothreitol (DTT), inhibited the induction of HO-1 by 15d-PGJ2. Finally, NAC and DTT exhibited significant inhibition of HO-1 mRNA and HO-1 promoter reporter activity induced by 15d-PGJ2. These results suggest that thiol antioxidant and reducing agents attenuate the expression of HO-1 induced by 15d-PGJ2, and that the cellular thiol-disulfide redox status may be linked to HO-1 activation.

Original languageEnglish
Pages (from-to)2451-2463
Number of pages13
JournalLife Sciences
Volume74
Issue number19
DOIs
Publication statusPublished - Mar 26 2004

Fingerprint

Heme Oxygenase-1
Reducing Agents
Sulfhydryl Compounds
Antioxidants
Dithiothreitol
Acetylcysteine
15-deoxy-delta(12,14)-prostaglandin J2
Chemical activation
Prostaglandin H2
Prostaglandin D2
Peroxisome Proliferator-Activated Receptors
Oxidative stress
Dinoprost
Eicosanoids
Docosahexaenoic Acids
Thromboxanes
Metabolites
Dinoprostone
Arachidonic Acid
Disulfides

Keywords

  • 15-Deoxy-Δ-prostaglandin J
  • Dithiothreitol
  • Glutathione
  • Heme oxygenase-1
  • N-Acetyl-L-cysteine

ASJC Scopus subject areas

  • Pharmacology

Cite this

Thiol antioxidant and thiol-reducing agents attenuate 15-deoxy-Δ 12,14-prostaglandin J2-induced heme oxygenase-1 expression. / Liu, Jean-Dean; Tsai, Shu Huei; Lin, Shyr Yi; Ho, Yuan Soon; Hung, Ling Fang; Pan, Shiann; Ho, Feng Ming; Lin, Chun Mao; Liang, Yu Chih.

In: Life Sciences, Vol. 74, No. 19, 26.03.2004, p. 2451-2463.

Research output: Contribution to journalArticle

@article{da4459da89fa456a837709303a108137,
title = "Thiol antioxidant and thiol-reducing agents attenuate 15-deoxy-Δ 12,14-prostaglandin J2-induced heme oxygenase-1 expression",
abstract = "Heme oxygenase-1 (HO-1) is induced as a beneficial and adaptive response in cells and tissues exposed to oxidative stress. Herein we examined how various eicosanoids affect the induction of HO-1, and the possible mechanism underlying 15-deoxy-Δ12,14- prostaglandin J2 (15d-PGJ2)-induced HO-1 expression. PGH2, PGD2 and its metabolites of the PGJ2 series, and PGA1 markedly induced the protein expression of HO-1. Arachidonic acid (AA), docosahexaenoic acid (DHA), PGE2, PGF2α, and thromboxane B 2 (TXB2) were shown to have no effect on the induction of HO-1. 15d-PGJ2 was the most potent activator achieving significance at 5 μM. Although 15d-PGJ2 significantly activated the MAPKs of JNK and ERK, the activation of JNK and ERK did not contribute to the induction of HO-1 as determined using transfection of dominant-negative plasmids and MAPKs inhibitors. Additional experiment indicated that 15d-PGJ2 induced HO-1 expression through peroxisome proliferator-activated receptor (PPAR)-independent pathway. 15d-PGJ2 significantly decreased the intracellular level of reduced glutathione; and the thiol antioxidant, N-acetyl-L-cysteine (NAC), and the thiol-reducing agent, dithiothreitol (DTT), inhibited the induction of HO-1 by 15d-PGJ2. Finally, NAC and DTT exhibited significant inhibition of HO-1 mRNA and HO-1 promoter reporter activity induced by 15d-PGJ2. These results suggest that thiol antioxidant and reducing agents attenuate the expression of HO-1 induced by 15d-PGJ2, and that the cellular thiol-disulfide redox status may be linked to HO-1 activation.",
keywords = "15-Deoxy-Δ-prostaglandin J, Dithiothreitol, Glutathione, Heme oxygenase-1, N-Acetyl-L-cysteine",
author = "Jean-Dean Liu and Tsai, {Shu Huei} and Lin, {Shyr Yi} and Ho, {Yuan Soon} and Hung, {Ling Fang} and Shiann Pan and Ho, {Feng Ming} and Lin, {Chun Mao} and Liang, {Yu Chih}",
year = "2004",
month = "3",
day = "26",
doi = "10.1016/j.lfs.2003.10.007",
language = "English",
volume = "74",
pages = "2451--2463",
journal = "Life Sciences",
issn = "0024-3205",
publisher = "Elsevier Inc.",
number = "19",

}

TY - JOUR

T1 - Thiol antioxidant and thiol-reducing agents attenuate 15-deoxy-Δ 12,14-prostaglandin J2-induced heme oxygenase-1 expression

AU - Liu, Jean-Dean

AU - Tsai, Shu Huei

AU - Lin, Shyr Yi

AU - Ho, Yuan Soon

AU - Hung, Ling Fang

AU - Pan, Shiann

AU - Ho, Feng Ming

AU - Lin, Chun Mao

AU - Liang, Yu Chih

PY - 2004/3/26

Y1 - 2004/3/26

N2 - Heme oxygenase-1 (HO-1) is induced as a beneficial and adaptive response in cells and tissues exposed to oxidative stress. Herein we examined how various eicosanoids affect the induction of HO-1, and the possible mechanism underlying 15-deoxy-Δ12,14- prostaglandin J2 (15d-PGJ2)-induced HO-1 expression. PGH2, PGD2 and its metabolites of the PGJ2 series, and PGA1 markedly induced the protein expression of HO-1. Arachidonic acid (AA), docosahexaenoic acid (DHA), PGE2, PGF2α, and thromboxane B 2 (TXB2) were shown to have no effect on the induction of HO-1. 15d-PGJ2 was the most potent activator achieving significance at 5 μM. Although 15d-PGJ2 significantly activated the MAPKs of JNK and ERK, the activation of JNK and ERK did not contribute to the induction of HO-1 as determined using transfection of dominant-negative plasmids and MAPKs inhibitors. Additional experiment indicated that 15d-PGJ2 induced HO-1 expression through peroxisome proliferator-activated receptor (PPAR)-independent pathway. 15d-PGJ2 significantly decreased the intracellular level of reduced glutathione; and the thiol antioxidant, N-acetyl-L-cysteine (NAC), and the thiol-reducing agent, dithiothreitol (DTT), inhibited the induction of HO-1 by 15d-PGJ2. Finally, NAC and DTT exhibited significant inhibition of HO-1 mRNA and HO-1 promoter reporter activity induced by 15d-PGJ2. These results suggest that thiol antioxidant and reducing agents attenuate the expression of HO-1 induced by 15d-PGJ2, and that the cellular thiol-disulfide redox status may be linked to HO-1 activation.

AB - Heme oxygenase-1 (HO-1) is induced as a beneficial and adaptive response in cells and tissues exposed to oxidative stress. Herein we examined how various eicosanoids affect the induction of HO-1, and the possible mechanism underlying 15-deoxy-Δ12,14- prostaglandin J2 (15d-PGJ2)-induced HO-1 expression. PGH2, PGD2 and its metabolites of the PGJ2 series, and PGA1 markedly induced the protein expression of HO-1. Arachidonic acid (AA), docosahexaenoic acid (DHA), PGE2, PGF2α, and thromboxane B 2 (TXB2) were shown to have no effect on the induction of HO-1. 15d-PGJ2 was the most potent activator achieving significance at 5 μM. Although 15d-PGJ2 significantly activated the MAPKs of JNK and ERK, the activation of JNK and ERK did not contribute to the induction of HO-1 as determined using transfection of dominant-negative plasmids and MAPKs inhibitors. Additional experiment indicated that 15d-PGJ2 induced HO-1 expression through peroxisome proliferator-activated receptor (PPAR)-independent pathway. 15d-PGJ2 significantly decreased the intracellular level of reduced glutathione; and the thiol antioxidant, N-acetyl-L-cysteine (NAC), and the thiol-reducing agent, dithiothreitol (DTT), inhibited the induction of HO-1 by 15d-PGJ2. Finally, NAC and DTT exhibited significant inhibition of HO-1 mRNA and HO-1 promoter reporter activity induced by 15d-PGJ2. These results suggest that thiol antioxidant and reducing agents attenuate the expression of HO-1 induced by 15d-PGJ2, and that the cellular thiol-disulfide redox status may be linked to HO-1 activation.

KW - 15-Deoxy-Δ-prostaglandin J

KW - Dithiothreitol

KW - Glutathione

KW - Heme oxygenase-1

KW - N-Acetyl-L-cysteine

UR - http://www.scopus.com/inward/record.url?scp=1442323937&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1442323937&partnerID=8YFLogxK

U2 - 10.1016/j.lfs.2003.10.007

DO - 10.1016/j.lfs.2003.10.007

M3 - Article

C2 - 14998722

AN - SCOPUS:1442323937

VL - 74

SP - 2451

EP - 2463

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

IS - 19

ER -