Activation of NAD(P)H oxidase by lipid hydroperoxides: Mechanism of oxidant-mediated smooth muscle cytotoxicity

Wei Gen Li, Lynn L. Stoll, James B. Rice, Shao Ping Xu, Francis J. Miller, Papri Chatterjee, Ling Hu, Larry W. Oberley, Arthur A. Spector, Neal L. Weintraub

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Oxidized lipids, such as 13-hydroperoxyoctadecadienoic acid (13-HPODE), have been implicated in the pathogenesis of atherosclerosis. 13-HPODE, a constituent of oxidized low-density lipoproteins, can induce cytotoxicity of vascular smooth muscle cells (SMC), which may facilitate plaque destabilization and/or rupture. 13-HPODE-induced cytotoxicity has been linked to oxidative stress, although the mechanisms by which this occurs are unknown. In the present study, we show that 13-HPODE and 9-HPODE (10-30 μM) increased superoxide (O 2 •- ) production and induced cytotoxicity in SMC. The 13-HPODE-induced increase in O 2 •- was blocked by transfecting the cells with antisense oligonucleotides against p22 phox , suggesting that the O 2 •- was produced by NAD(P)H oxidase. Similar concentrations of the corresponding HPODE reduction products, 13-hydroxyoctadecadienoic acid (13-HODE) and 9-HODE, neither increased O 2 •- production nor induced cytotoxicity, while 4-hydroxy nonenal (4-HNE), an unsaturated aldehyde lipid peroxidation product, induced cytotoxicity without increasing O 2 •- production. Treatment with superoxide dismutase or Tiron to scavenge O 2 •- , or transfection with p22 phox antisense oligonucleotides to inhibit O 2 •- production, attenuated 13-HPODE-induced cytotoxicity, but not that induced by 4-HNE. These findings suggest that activation of NAD(P)H oxidase, and production of O 2 •- , play an important role in lipid hydroperoxide-induced smooth muscle cytotoxicity.

Original languageEnglish (US)
Pages (from-to)937-946
Number of pages10
JournalFree Radical Biology and Medicine
Volume34
Issue number7
DOIs
StatePublished - Apr 1 2003

Fingerprint

NADPH Oxidase
Lipid Peroxides
Cytotoxicity
Oxidants
Smooth Muscle
Muscle
Chemical activation
Acids
Antisense Oligonucleotides
Smooth Muscle Myocytes
1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt
Lipids
Oxidative stress
Vascular Smooth Muscle
Aldehydes
Superoxides
Lipid Peroxidation
Superoxide Dismutase
Transfection
Rupture

Keywords

  • 13-HPODE
  • Atherosclerosis
  • Free radicals
  • NAD(P)H oxidase
  • Smooth muscle cells
  • Superoxide

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Activation of NAD(P)H oxidase by lipid hydroperoxides : Mechanism of oxidant-mediated smooth muscle cytotoxicity. / Li, Wei Gen; Stoll, Lynn L.; Rice, James B.; Xu, Shao Ping; Miller, Francis J.; Chatterjee, Papri; Hu, Ling; Oberley, Larry W.; Spector, Arthur A.; Weintraub, Neal L.

In: Free Radical Biology and Medicine, Vol. 34, No. 7, 01.04.2003, p. 937-946.

Research output: Contribution to journalArticle

Li, WG, Stoll, LL, Rice, JB, Xu, SP, Miller, FJ, Chatterjee, P, Hu, L, Oberley, LW, Spector, AA & Weintraub, NL 2003, 'Activation of NAD(P)H oxidase by lipid hydroperoxides: Mechanism of oxidant-mediated smooth muscle cytotoxicity', Free Radical Biology and Medicine, vol. 34, no. 7, pp. 937-946. https://doi.org/10.1016/S0891-5849(03)00032-7
Li, Wei Gen ; Stoll, Lynn L. ; Rice, James B. ; Xu, Shao Ping ; Miller, Francis J. ; Chatterjee, Papri ; Hu, Ling ; Oberley, Larry W. ; Spector, Arthur A. ; Weintraub, Neal L. / Activation of NAD(P)H oxidase by lipid hydroperoxides : Mechanism of oxidant-mediated smooth muscle cytotoxicity. In: Free Radical Biology and Medicine. 2003 ; Vol. 34, No. 7. pp. 937-946.
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abstract = "Oxidized lipids, such as 13-hydroperoxyoctadecadienoic acid (13-HPODE), have been implicated in the pathogenesis of atherosclerosis. 13-HPODE, a constituent of oxidized low-density lipoproteins, can induce cytotoxicity of vascular smooth muscle cells (SMC), which may facilitate plaque destabilization and/or rupture. 13-HPODE-induced cytotoxicity has been linked to oxidative stress, although the mechanisms by which this occurs are unknown. In the present study, we show that 13-HPODE and 9-HPODE (10-30 μM) increased superoxide (O 2 •- ) production and induced cytotoxicity in SMC. The 13-HPODE-induced increase in O 2 •- was blocked by transfecting the cells with antisense oligonucleotides against p22 phox , suggesting that the O 2 •- was produced by NAD(P)H oxidase. Similar concentrations of the corresponding HPODE reduction products, 13-hydroxyoctadecadienoic acid (13-HODE) and 9-HODE, neither increased O 2 •- production nor induced cytotoxicity, while 4-hydroxy nonenal (4-HNE), an unsaturated aldehyde lipid peroxidation product, induced cytotoxicity without increasing O 2 •- production. Treatment with superoxide dismutase or Tiron to scavenge O 2 •- , or transfection with p22 phox antisense oligonucleotides to inhibit O 2 •- production, attenuated 13-HPODE-induced cytotoxicity, but not that induced by 4-HNE. These findings suggest that activation of NAD(P)H oxidase, and production of O 2 •- , play an important role in lipid hydroperoxide-induced smooth muscle cytotoxicity.",
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T2 - Mechanism of oxidant-mediated smooth muscle cytotoxicity

AU - Li, Wei Gen

AU - Stoll, Lynn L.

AU - Rice, James B.

AU - Xu, Shao Ping

AU - Miller, Francis J.

AU - Chatterjee, Papri

AU - Hu, Ling

AU - Oberley, Larry W.

AU - Spector, Arthur A.

AU - Weintraub, Neal L.

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Y1 - 2003/4/1

N2 - Oxidized lipids, such as 13-hydroperoxyoctadecadienoic acid (13-HPODE), have been implicated in the pathogenesis of atherosclerosis. 13-HPODE, a constituent of oxidized low-density lipoproteins, can induce cytotoxicity of vascular smooth muscle cells (SMC), which may facilitate plaque destabilization and/or rupture. 13-HPODE-induced cytotoxicity has been linked to oxidative stress, although the mechanisms by which this occurs are unknown. In the present study, we show that 13-HPODE and 9-HPODE (10-30 μM) increased superoxide (O 2 •- ) production and induced cytotoxicity in SMC. The 13-HPODE-induced increase in O 2 •- was blocked by transfecting the cells with antisense oligonucleotides against p22 phox , suggesting that the O 2 •- was produced by NAD(P)H oxidase. Similar concentrations of the corresponding HPODE reduction products, 13-hydroxyoctadecadienoic acid (13-HODE) and 9-HODE, neither increased O 2 •- production nor induced cytotoxicity, while 4-hydroxy nonenal (4-HNE), an unsaturated aldehyde lipid peroxidation product, induced cytotoxicity without increasing O 2 •- production. Treatment with superoxide dismutase or Tiron to scavenge O 2 •- , or transfection with p22 phox antisense oligonucleotides to inhibit O 2 •- production, attenuated 13-HPODE-induced cytotoxicity, but not that induced by 4-HNE. These findings suggest that activation of NAD(P)H oxidase, and production of O 2 •- , play an important role in lipid hydroperoxide-induced smooth muscle cytotoxicity.

AB - Oxidized lipids, such as 13-hydroperoxyoctadecadienoic acid (13-HPODE), have been implicated in the pathogenesis of atherosclerosis. 13-HPODE, a constituent of oxidized low-density lipoproteins, can induce cytotoxicity of vascular smooth muscle cells (SMC), which may facilitate plaque destabilization and/or rupture. 13-HPODE-induced cytotoxicity has been linked to oxidative stress, although the mechanisms by which this occurs are unknown. In the present study, we show that 13-HPODE and 9-HPODE (10-30 μM) increased superoxide (O 2 •- ) production and induced cytotoxicity in SMC. The 13-HPODE-induced increase in O 2 •- was blocked by transfecting the cells with antisense oligonucleotides against p22 phox , suggesting that the O 2 •- was produced by NAD(P)H oxidase. Similar concentrations of the corresponding HPODE reduction products, 13-hydroxyoctadecadienoic acid (13-HODE) and 9-HODE, neither increased O 2 •- production nor induced cytotoxicity, while 4-hydroxy nonenal (4-HNE), an unsaturated aldehyde lipid peroxidation product, induced cytotoxicity without increasing O 2 •- production. Treatment with superoxide dismutase or Tiron to scavenge O 2 •- , or transfection with p22 phox antisense oligonucleotides to inhibit O 2 •- production, attenuated 13-HPODE-induced cytotoxicity, but not that induced by 4-HNE. These findings suggest that activation of NAD(P)H oxidase, and production of O 2 •- , play an important role in lipid hydroperoxide-induced smooth muscle cytotoxicity.

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KW - Atherosclerosis

KW - Free radicals

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KW - Superoxide

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