Quinone compounds regulate the level of ROS production by the NADPH oxidase Nox4
2013 (English)In: Biochemical Pharmacology, ISSN 0006-2952, E-ISSN 1356-1839, Vol. 85, no 11, 1644-1654 p.Article in journal (Refereed) Published
NADPH oxidase Nox4 is expressed in a wide range of tissues and plays a role in cellular signaling by providing reactive oxygen species (ROS) as intracellular messengers. Nox4 oxidase activity is thought to be constitutive and regulated at the transcriptional level; however, we challenge this point of view and suggest that specific quinone derivatives could modulate this activity. In fact, we demonstrated a significant stimulation of Nox4 activity by 4 quinone derivatives (AA-861, tBuBHQ tBuBQ and duroquinone) observed in 3 different cellular models, HEK293E, T-REx (TM), and chondrocyte cell lines. Our results indicate that the effect is specific toward Nox4 versus Nox2. Furthermore, we showed that NAD(P)H:quinone oxidoreductase (NQO1) may participate in this stimulation. Interestingly, Nox4 activity is also stimulated by reducing agents that possibly act by reducing the disulfide bridge (Cys226, Cys270) located in the extracellular E-loop of Nox4. Such model of Nox4 activity regulation could provide new insight into the understanding of the molecular mechanism of the electron transfer through the enzyme, i.e., its potential redox regulation, and could also define new therapeutic targets in diseases in which quinones and Nox4 are implicated.
Place, publisher, year, edition, pages
Elsevier, 2013. Vol. 85, no 11, 1644-1654 p.
NADPH oxidase Nox4, NAD(P)H:quinone oxidoreductase NQO1, Quinones, Redox regulation of Nox, Reactive oxygen species (ROS)
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-95506DOI: 10.1016/j.bcp.2013.03.023ISI: 000319491900010OAI: oai:DiVA.org:liu-95506DiVA: diva2:635748
Funding Agencies|Ministere de lEnseignement superieur de la recherche et la technologie, Paris, France||CNRS Institute||Association pour la Recherche contre le Cancer (ARC), Paris, France||Region Rhone-Alpes||programme ARCUS, France/Chine||CGD research Trust, UK||Groupement des Entreprises Francaises de la Lutte contre le Cancer, delegation de Grenoble||UFR de Medecine, Universite Joseph Fourier, Grenoble||Direction Regionale de la Recherche Clinique, Center Hospitalier Universitaire, Grenoble||2013-07-052013-07-052014-08-21Bibliographically approved