Analyses of Bone Marrow and Blood Samples From Healthy Volunteers: Focus on the redOx Metabolism

Overview

Oxidative stress is defined by an excess of reactive oxygen species (reactive oxygen species or ROS) in cells. ROS are essential to cell life (proliferation, differentiation), including kinase activity via inhibition of phosphatases. Very low levels of ROS are observed in quiescent cells, including hematopoietic stem cells. Conversely, an excess of ROS can induce DNA damage that may lead to the destruction of the cell. The level of ROS in cells is the result of production (mainly the NADPHoxydase and the mitochondrial respiratory chain) and their disposal via antioxidant enzymes. The hematology team of the university hospital of Tours (France) found that certain antioxidant enzymes are essential for the self-renewal of normal and leukemic cells such as glutathione peroxidase-3 (Herault O et al, J Exp Med 2012, 209:895). Their expression is modified in hematological diseases (patent WO2012085188A1 / 2012-06-28 and FR1000267310 / 2014-11-27). Age potentially affects the level of expression of antioxidant genes, since it was established a decrease in glutathione peroxidase activity in women over 65 years (Sara E, J Gerontol A Biol Sci Med Sci 2008 63: 505). The study HEALTHOX will determine the impact of age on the oxidative metabolism of normal hematopoietic cells, and in particular the expression of antioxidant genes. It will provide a reference for analyzing disturbances of oxidative metabolism in blood diseases. The main objective is the comparison of peripheral blood and bone marrow cells depending from 3 groups of healthy volunteers: 18-39 years, 40-59 years and 60-85 years. The level of ROS and the expression of genes encoding the major antioxidant enzymes involved in the regulation of oxidative stress will be studied. The secondary objectives are to create a cell bank (blood and marrow), a blood plasma bank and a cDNA library (blood and marrow) from healthy volunteers.