CHARACTERIZATION OF THE EXPRESSION PATTERN OF THE THIOREDOXINS

JUAN I. ROMERO(A), PABLO GALEANO(A), MARIA E. HANSCHMANN(B), CHRISTOPHER H. LILLIG(B), FRANCISCO CAPANI

Congreso; Segundo Encuentro de la Sociedad Argentina de Microscopia; 2012

Brain damage resulting from a combination of hypoxia and reduced cerebral blood flow (ischemia) in the fetus and newborn infant remains a major cause of death and disability in children, being cerebral palsy, mental retardation, and epilepsy among the most common complications [1][2][3][4]. The incidence of severe perinatal asphyxia is estimated of about 1/1000 live births in developed countries, having an incidence of 5–10/1000 live births in developing countries [5]. The production of reactive oxygen species (ROS) has been proposed as an important cause of neuronal death and consequently brain damage after ischemia–reperfusion [6]. Currently, several therapeutic approaches for the destruction of oxygen free radicals generated during and following hypoxia–ischemia have been proposed. Such as the administration of specific enzymes known to degrade highly reactive radicals to a non-reactive component, free radical inhibitors, and scavengers [5]. At present, no individual neuroprotective agents have been proven safe and effective for the protection of neonates from neurological sequels after a hypoxic-ischemic insult. The insight into the biochemical and cellular mechanisms of neuronal injury with perinatal hypoxia ischemia helps to provide interventions to interrupt those deleterious cascades, principally focusing on the potential effects of free radical scavengers [7]. Nowadays, we look at Thioredoxins (Trxs) a crucial protein family for antioxidative defense, the modulation of intra- and extracellular signalling pathways, the regulation of transcription factors, and the modulation of immune response, and new functions of Trxs are described almost on a weekly basis [8]. In the present work, we study the differential expression of the oxidoreductases of the Trxs of proteins, and their role in the cellular response to oxidative stress in a modified model of perinatal hypoxic-ischemia developed by Rice (1981) [1] and Levine (1960) [9]. At a molecular level we have observed several remarkable differences in both abundance and regional distribution of Trxs (this family) of proteins at different times. Combining Western Blot and light microscopy analysis, we have observed some remarkable differential expression of these proteins in the most vulnerable areas of the brain to hypoxia-ischemia. REFERENCES [1] Rice JE 3rd, Vannucci RC, Brierley JB. The influence of immaturity on hypoxic-ischemic brain damage in the rat. Ann Neurol. 1981 Feb;9(2):131-41. [2] Paneth N. The causes of cerebral palsy. Recent evidence. Clin Invest Med 1993; 16: 95-102. [3] Nelson KB, Grether JK. Potentially asphyxiating conditions and spastic cerebral palsy in infants of normal birth weight. Am J Obstet Gynecol 1998; 179: 507-13. [4] Titomanlio L, Kavelaars A, Dalous J, Mani S, El Ghouzzi V, Heijnen C, Baud O, Gressens P. Stem cell therapy for neonatal brain injury: Perspectives and Challenges. Ann Neurol. 2011 Nov;70(5):698-712 [5] McGuire W. Perinatal asphyxia. Clin Evid. 2007 Nov 7;2007. pii: 0320. (pp. 511–519) [6] Capani F, Loidl CF, Aguirre F, Piehl L, Facorro G, Hager A, De Paoli T, Farach H, Pecci-Saavedra J. Changes in reactive oxygen species (ROS) production in rat brain during global perinatal asphyxia: an ESR study. Brain Res. 2001 Sep 28;914(1-2):204-7. [7] Lai MC, Yang SN. Perinatal hypoxic-ischemic encephalopathy. J Biomed Biotechnol. 2011;2011:609813. Epub 2010 Dec 13. [8] Lillig CH, Holmgren A. Thioredoxin and related molecules--from biology to health and disease. Antioxid Redox Signal. 2007 Jan;9(1):25-47. [9] levine S. Anoxic-ischemic encephalopathy in rats. Am J Pathol. 1960 Jan;36:1-17. Keywords: Perinatal hypoxia-ischemia, tioredoxins, CNS