Thioredoxin-1/peroxiredoxin-1 as sensors of oxidative stress mediated by NADPH oxidase activity in atherosclerosis

Julio Madrigal-Matute, Carlos Ernesto Fernandez-Garcia, Luis Miguel Blanco-Colio, Elena Burillo, Ana Fortuño, Roxana Martinez-Pinna, Patricia Llamas-Granda, Oscar Beloqui, Jesus Egido, Guillermo Zalba, José Luis Martin-Ventura

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Abstract To assess the potential association between TRX-1/PRX-1 and NADPH oxidase (Nox) activity in vivo and in vitro, TRX-1/PRX-1 levels were assessed by ELISA in 84 asymptomatic subjects with known phagocytic NADPH oxidase activity and carotid intima-media thickness (IMT). We found a positive correlation between TRX-1/PRX-1 and NADPH oxidase-dependent superoxide production (r=0.48 and 0.47; p<0.001 for both) and IMT (r=0.31 and 0.36; p<0.01 for both) adjusted by age and sex. Moreover, asymptomatic subjects with plaques have higher PRX-1 and TRX plasma levels (p<0.01 for both). These data were confirmed in a second study in which patients with carotid atherosclerosis showed higher PRX-1 and TRX plasma levels than healthy subjects (p<0.001 for both). In human atherosclerotic plaques, the NADPH oxidase subunit p22phox colocalized with TRX-1/PRX-1 in macrophages (immunohistochemistry). In monocytes and macrophages, phorbol 12-myristate 13-acetate (PMA) induced NADPH activation and TRX-1/PRX-1 release to the extracellular medium, with a concomitant decrease in their intracellular levels, which was reversed by the NADPH inhibitor apocynin (Western blot). In loss-of-function experiments, genetic silencing of the NADPH oxidase subunit Nox2 blocked PMA-induced intracellular TRX-1/PRX-1 downregulation in macrophages. Furthermore, the PMA-induced release of TRX-1/PRX-1 involves the modulation of their redox status and exosome-like vesicles. TRX-1/PRX-1 levels are associated with NADPH oxidase-activity in vivo and in vitro. These data could suggest a coordinated antioxidant response to oxidative stress in atherothrombosis.

Original languageEnglish (US)
Article number12461
Pages (from-to)352-361
Number of pages10
JournalFree Radical Biology and Medicine
Volume86
DOIs
StatePublished - Jul 25 2015

Fingerprint

Peroxiredoxins
Thioredoxins
Oxidative stress
NADPH Oxidase
Macrophages
Atherosclerosis
Oxidative Stress
Acetates
Sensors
NADP
Exosomes
Plasmas
Carotid Intima-Media Thickness
Carotid Artery Diseases
Atherosclerotic Plaques
Superoxides
Oxidation-Reduction
Monocytes
Healthy Volunteers
Down-Regulation

Keywords

  • Atherosclerosis
  • Free radicals
  • NADPH oxidase
  • Oxidative stress
  • Peroxiredoxin
  • Thioredoxin

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Madrigal-Matute, J., Fernandez-Garcia, C. E., Blanco-Colio, L. M., Burillo, E., Fortuño, A., Martinez-Pinna, R., ... Martin-Ventura, J. L. (2015). Thioredoxin-1/peroxiredoxin-1 as sensors of oxidative stress mediated by NADPH oxidase activity in atherosclerosis. Free Radical Biology and Medicine, 86, 352-361. [12461]. https://doi.org/10.1016/j.freeradbiomed.2015.06.001

Thioredoxin-1/peroxiredoxin-1 as sensors of oxidative stress mediated by NADPH oxidase activity in atherosclerosis. / Madrigal-Matute, Julio; Fernandez-Garcia, Carlos Ernesto; Blanco-Colio, Luis Miguel; Burillo, Elena; Fortuño, Ana; Martinez-Pinna, Roxana; Llamas-Granda, Patricia; Beloqui, Oscar; Egido, Jesus; Zalba, Guillermo; Martin-Ventura, José Luis.

In: Free Radical Biology and Medicine, Vol. 86, 12461, 25.07.2015, p. 352-361.

Research output: Contribution to journalArticle

Madrigal-Matute, J, Fernandez-Garcia, CE, Blanco-Colio, LM, Burillo, E, Fortuño, A, Martinez-Pinna, R, Llamas-Granda, P, Beloqui, O, Egido, J, Zalba, G & Martin-Ventura, JL 2015, 'Thioredoxin-1/peroxiredoxin-1 as sensors of oxidative stress mediated by NADPH oxidase activity in atherosclerosis', Free Radical Biology and Medicine, vol. 86, 12461, pp. 352-361. https://doi.org/10.1016/j.freeradbiomed.2015.06.001
Madrigal-Matute, Julio ; Fernandez-Garcia, Carlos Ernesto ; Blanco-Colio, Luis Miguel ; Burillo, Elena ; Fortuño, Ana ; Martinez-Pinna, Roxana ; Llamas-Granda, Patricia ; Beloqui, Oscar ; Egido, Jesus ; Zalba, Guillermo ; Martin-Ventura, José Luis. / Thioredoxin-1/peroxiredoxin-1 as sensors of oxidative stress mediated by NADPH oxidase activity in atherosclerosis. In: Free Radical Biology and Medicine. 2015 ; Vol. 86. pp. 352-361.
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AU - Blanco-Colio, Luis Miguel

AU - Burillo, Elena

AU - Fortuño, Ana

AU - Martinez-Pinna, Roxana

AU - Llamas-Granda, Patricia

AU - Beloqui, Oscar

AU - Egido, Jesus

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AU - Martin-Ventura, José Luis

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N2 - Abstract To assess the potential association between TRX-1/PRX-1 and NADPH oxidase (Nox) activity in vivo and in vitro, TRX-1/PRX-1 levels were assessed by ELISA in 84 asymptomatic subjects with known phagocytic NADPH oxidase activity and carotid intima-media thickness (IMT). We found a positive correlation between TRX-1/PRX-1 and NADPH oxidase-dependent superoxide production (r=0.48 and 0.47; p<0.001 for both) and IMT (r=0.31 and 0.36; p<0.01 for both) adjusted by age and sex. Moreover, asymptomatic subjects with plaques have higher PRX-1 and TRX plasma levels (p<0.01 for both). These data were confirmed in a second study in which patients with carotid atherosclerosis showed higher PRX-1 and TRX plasma levels than healthy subjects (p<0.001 for both). In human atherosclerotic plaques, the NADPH oxidase subunit p22phox colocalized with TRX-1/PRX-1 in macrophages (immunohistochemistry). In monocytes and macrophages, phorbol 12-myristate 13-acetate (PMA) induced NADPH activation and TRX-1/PRX-1 release to the extracellular medium, with a concomitant decrease in their intracellular levels, which was reversed by the NADPH inhibitor apocynin (Western blot). In loss-of-function experiments, genetic silencing of the NADPH oxidase subunit Nox2 blocked PMA-induced intracellular TRX-1/PRX-1 downregulation in macrophages. Furthermore, the PMA-induced release of TRX-1/PRX-1 involves the modulation of their redox status and exosome-like vesicles. TRX-1/PRX-1 levels are associated with NADPH oxidase-activity in vivo and in vitro. These data could suggest a coordinated antioxidant response to oxidative stress in atherothrombosis.

AB - Abstract To assess the potential association between TRX-1/PRX-1 and NADPH oxidase (Nox) activity in vivo and in vitro, TRX-1/PRX-1 levels were assessed by ELISA in 84 asymptomatic subjects with known phagocytic NADPH oxidase activity and carotid intima-media thickness (IMT). We found a positive correlation between TRX-1/PRX-1 and NADPH oxidase-dependent superoxide production (r=0.48 and 0.47; p<0.001 for both) and IMT (r=0.31 and 0.36; p<0.01 for both) adjusted by age and sex. Moreover, asymptomatic subjects with plaques have higher PRX-1 and TRX plasma levels (p<0.01 for both). These data were confirmed in a second study in which patients with carotid atherosclerosis showed higher PRX-1 and TRX plasma levels than healthy subjects (p<0.001 for both). In human atherosclerotic plaques, the NADPH oxidase subunit p22phox colocalized with TRX-1/PRX-1 in macrophages (immunohistochemistry). In monocytes and macrophages, phorbol 12-myristate 13-acetate (PMA) induced NADPH activation and TRX-1/PRX-1 release to the extracellular medium, with a concomitant decrease in their intracellular levels, which was reversed by the NADPH inhibitor apocynin (Western blot). In loss-of-function experiments, genetic silencing of the NADPH oxidase subunit Nox2 blocked PMA-induced intracellular TRX-1/PRX-1 downregulation in macrophages. Furthermore, the PMA-induced release of TRX-1/PRX-1 involves the modulation of their redox status and exosome-like vesicles. TRX-1/PRX-1 levels are associated with NADPH oxidase-activity in vivo and in vitro. These data could suggest a coordinated antioxidant response to oxidative stress in atherothrombosis.

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