Expression of peroxiredoxins and thioredoxins in the mouse spinal cord during embryonic development

Abstract

Reactive oxygen and nitrogen species (ROS/RNS) are natural byproducts of cellular metabolism. Although these molecules are deleterious at high concentrations, moderate levels of ROS/RNS are essential for normal cell function and take part in numerous cellular processes. The regulation of ROS/RNS is largely attended by peroxiredoxins (Prdxs) and their main reductants, thioredoxins (Trxs). Through their oxidoreductase activities, the members of the Trx/Prdx system can also affect certain cellular processes, notably many implicated in central nervous system (CNS) development. Although several studies have investigated the expression of Prdxs and Trxs in mouse, rat, and human adult CNS, few data are available concerning embryonic stages. In this work, we use immunofluorescence analyses to study the distribution of these enzymes during prenatal mouse spinal cord development. Our results highlight several patterns that contrast with available data for the adult. Indeed, Prdx1, Prdx4, and Prdx6, which are expressed in glial cells in the adult CNS, present clear neuronal localization in mouse spinal cord during embryonic development. Additionally, Prdx1, Prdx2, and to a lesser extent Prdx4, Prdx6, and Trx1 are localized mainly in the nucleus of neural cells. Finally, we identified a consistent, intense expression of all Prdxs and Trxs in groups of cells located in ventral regions of the spinal cord that express motor neuronal markers. These striking expression patterns suggest novel functions of these enzymes at these stages and offer clues to the role of the Trx/Prdx system during embryonic development of the spinal cord.

Peroxiredoxin1, a novel regulator of pronephros development, influences retinoic acid and Wnt signaling by controlling ROS levels

“…Prdx1 also plays a critical role in the progression of different types of cancer, and several studies have proposed therapies aimed at halting or slowing down cancer growth 16 , 22 . In addition to its protective effects against reactive oxygen species (ROS) or oxidative stress, Prdx1 also influences downstream signaling pathways during organogenesis 24 .…”

Thioredoxin-2 Modulates Neuronal Programmed Cell Death in the Embryonic Chick Spinal Cord in Basal and Target-Deprived Conditions

“…The Trx2 antibody used in this work was previously validated in the embryonic mouse spinal cord [ 20 ]. In order to validate the antibody in chick embryo spinal cord, immunofluorescence assays using the antibody or the antibody preadsorbed with the antigen were also performed on E4.5 and E6.5 chick embryos ( Fig 1A–1D ).…”

“…In addition, both ROS and antioxidant enzymes such as Trx2 have been directly or indirectly linked to the onset and signaling cascades implicated in cell death pathways [ 35 – 37 ]. Coincidentally, Trx2 is also strongly expressed in mouse motor neurons at the developmental stages at which this motor neuron PCD takes places [ 20 ]. These data could therefore indicate an implication of Trx2 in the regulation of this process.…”

“…Polyclonal rabbit antibody directed to human Trx2 used in this work was previously validated in the embryonic mouse spinal cord [ 20 ]. Validation of this antibody in chick CNS was confirmed through the reduction of signal observed in Western blotting (data not shown) and immunofluorescence after preadsorption with recombinant human Trx2 ( Fig 1A–1D ).…”

“…In previous studies completed in our laboratory, we showed that Prdxs and Trxs are highly expressed in spinal cord motor neurons during embryonic development in the mouse [ 20 ]. Notably, Trx2 expression was particularly high in motor neurons at developmental stages coinciding with the onset of developmental PCD of motor neurons.…”