Molecular and Cellular Biology

NADPH Oxidases

MOLECULAR AND CELLULAR BIOLOGY LABORATORY

From H2O2 generator DUOX to oxidative stress and cancer development.

Welcome to the DUOX Lab Web site! 

 

Our research group is part of the Institute of Interdisciplinary Research, IRIBHM (Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire). This research center is localized at the Medical School of the University of Brussels (Université Libre de Bruxelles, ULB).

 

thyroid

Hydrogen peroxide (H2O2) is a highly reactive chemical molecule originally considered as an antibacterial agent. In excess, H2Oinduces an oxidative stress responsible for different pathologies like cardiovascular disease, neurodegeneration, tumorigenesis or ageing. It is now widely accepted that many cell types other than the phagocytes produce reactive oxygen species (ROS).

The thyroid tissue generates massive amounts of H2Othat are required for the biosynthesis of thyroid hormones T3/T4. In 2000, we discovered and characterized the molecular nature of the molecules responsible for this H2Ogenerating system: the DUOX1 and DUOX2 enzymes. These proteins belong to a new family of proteins, the NADPH-oxidases, presenting a catalytic domain involved in ROS generation. The DUOX are also present at the mucosal surface of the digestive and respiratory epithelia.

  

 

 

 

 

 

 

HE_Thyrocytes

Our multidisciplinary projects aim to better characterize the function of these new oxidases and to study their physiological roles in humans and in DUOX knock-out mouse models. By molecular and biochemical approaches, we explore the mechanisms involved in the maturation and the enzymatic activity of these oxidases.

Up to 50% of the population above 60 years old present thyroid nodules and 5% of these nodules will degenerate into cancers. Irradiation is not responsible for the majority of thyroid tumors. We have recently demonstrated that H2Ocauses DNA double-strand breaks that are considered as one of the primary cause of cancer. These data support the hypothesis that H2Ogeneration by the thyroid metabolism could play a role in mutagenesis particularly in case of antioxidant deficiency. A better understanding of the biochemistry of these new H2Ogenerators would have a major impact in the comprehension of the pathophysiology of these diseases.

                                 logoIRIBHM     sceau_ULB     FNRS     Erasme     Fondation_contre_le_cancer     Belspo