Effects of Hypoxia on Stress Proteins in the Piglet Brain at Birth

Abstract

Newborn piglets were submitted to normobaric hypoxia (5% O 2 , 95% N 2 ) for either 1 or 4 h. The effects of hypoxia on the neonatal brain were characterized through a time-course analysis of levels of various proteins such as heat shock proteins (HSP27, 70, and 90), hypoxia inducible factor-1␣ (HIF-1␣), neuronal nitric oxide synthase (nNOS), hemeoxygenase-2 (HO-2), and caspase-3. The expression of these proteins was determined at different stages of recovery up to 72 h in cerebellum, cortex, and hippocampus by Western blot analysis in hypoxic maintained animals that were made hypoxic at either 20 or 37°C. In all regions of the brain, HIF-1␣ and HSP27 expression were strongly increased until 22 h of recovery. No significant changes were observed for HSP70, HSP90, and HO-2. A small elevation of expression of nNOS was observed at early stages in the cerebellum and the cortex with no change in the hippocampus.Expression of caspase 3 was strongly increased in the cortex 24 and 48 h after hypoxia but unchanged in the hippocampus. These results are presented in terms of the porcine model of nonischemic hypoxia and its delayed neuronal effects on the cerebral outcome. Because of their recently established biochemical and functional interactions, the expression of the main HSPs, HIF-1␣, nNOS, and caspase-3 after hypoxia are delineated. Perinatal asphyxia and hypoxia are common causes of neonatal morbidity. Among survivors, several disabilities are observed, including pulmonary, renal, cardiac, and encephalopathic dysfunction (1,2). Asphyxia at birth can result in severe auditory problems for the infant (3,4) as well as increased risks of amnesia (5) and schizophrenia presenting at different stages (6). Outcomes of asphyxia and/or hypoxia-ischemia can also result in cognitive impairment and developmental delay for the infants (7). Such severe sequelae of birth hypoxia are apparent early at the molecular level in the brain. Impairment as a result of hypoxia includes the transient reduction of GABA receptor numbers (8), altered expression of glutamate transporters (9), and/or a disruption of myelin gene expression (10). Because of the severe consequences of hypoxia at birth time on cerebral functions, a better characterization of molecular changes within the hypoxic neonatal brain is of crucial importance.The study of the expression and induction of stress proteins in the hypoxic brain is of particular interest because heat shock proteins (HSPs) have cytoprotective properties and are induced after a variety of stressors, such as elevated temperature (11-13) or hypoxia (14). HSPs are classified in three large families according to their molecular weights (11-13). However, very few studies have described the developmental changes of HSPs at the time of birth (15-17). The protective role of HSPs against hypoxia at birth has not been investigated, although in the brain, these proteins are known to be cytoprotective after hypoxia-ischemia (18,19). Other proteins induced by neonatal hypoxic stress are also of interest. Hypoxia i...

Effects of hypoxia on stress proteins in the piglet heart at birth

“…Statistical analysis was performed as follows: after global analysis of variance, the mean values were compared as indicated in the legends by a nonparametric analysis for variance (Kruskal-Wallis test). When significant, 2 by 2 comparisons were made according to Conover as already described (Conover 1980;Chiral et al 2004) for the highly significant multiple comparison test with P values less than 0.01 indicating significance.…”

EXPOSURE TO 2.45 GHz MICROWAVE RADIATION PROVOKES CEREBRAL CHANGES IN INDUCTION OF HSP-90 α/β HEAT SHOCK PROTEIN IN RAT.

“…Other stress-related stimuli such as fever, convulsions [20], drugs (amphetamine or LSD) [21], injury and neurodegenerative diseases [22] cause modifications in the basal levels of HSP-90. An increase in HSP-90 in neuronal subpopulations [23] and/or its activation in new non neuronal glial and microglial cell populations [24] indicates participation by this protein in neuroprotective mechanisms [25], oxidative stress [26] and anti-apoptic activity [27,28].…”

Heat Shock Protein 70 Expression in Juvenile Eastern Oysters,Crassostrea virginica(Gmelin, 1791), Exposed to Anoxic Conditions

“…1 and 2). Although some studies have shown induction of HSP 70 messenger RNA after exposure to anoxia or hypoxia, others have shown little or no response of HSP 70 to hypoxia (Chiral et al 2004, Cara et al 2005, Sarkis et al 2005. Facultative anaerobiosis and metabolic arrest during anoxia or hypoxia in molluscs including Crassostrea species is a well-known strategy for survival (Hochachka & Mustafa 1973, Storey 1993, and Oysters were exposed to normoxia and anoxia.…”