Expression of Transcription Factors in the Brain of Rats with Perinatal Asphyxia

Abstract

No information is available on transcription factors (TF), the main regulators of gene expression, in perinatal asphyxia (PA), and as pathomechanisms in PA are different, data on TFs from ischemia or hypoxia cannot be simply extrapolated to PA, and no studies have been reported to show an expressional pattern or the concerted action of TFs. We, therefore, used a gene-hunting technique, subtractive hybridization, to show sequences different in brains of normoxic and perinatally asphyxiated (10 and 20 min of asphyxia) rats. These subtracted sequences were identified by gene bank and assigned to individual genes. At 10 min of PA the TFs NFI/CAAT-binding protein, NF-kappa-B p65, N-myc, basic helix loop helix protein D82868, and c-myc intron binding protein were upregulated. At 20 min of PA the TFs SOX4 and neuronal death factor were upregulated, whereas the TFs c-maf, PEBP major transcription factor, brn-2, homeodomain protein Af004431, and zinc finger transcriptional factor M65008 were downregulated. The biological meaning of our findings is the demonstration of a pathophysiological pattern of TFs including POU, zinc finger, homeodomain, and basic helix-loop helix motifs in PA, proposing pathomechanisms for brain damage from PA, explaining transcriptional changes in general (as, e.g., NF-kappa-B p65, etc.) or in specific terms (as, e.g., neuronal death factor).

Perinatal asphyxia: current status and approaches towards neuroprotective strategies, with focus on sentinel proteins

“…Suppression and/or over-activation of gene expression occurs immediately or during the re-oxygenation period following perinatal asphyxia (Labudova et al 1999; Seidl et al 2000; Mosgoeller et al 2000; Lubec et al 2002). When the DNA integrity is compromised, a number of sentinel proteins are activated, including (i) poly(ADP-ribose) polymerases (PARPs) (Amé et al 2004); (ii) X-ray Cross-Complementing Factor 1 (XRCC1) (Green et al 1992); (iii) DNA ligase IIIα (Leppard et al 2003); (iv) DNA polymerase β (Wilson 1998; Mishra et al 2003); (v) Excision Repair Cross-Complementing Rodent Repair Group 2 (ERCC2) (Sung et al 1993; Chiappe-Gutierrez et al 1998; Lubec et al 2002) and (vi) DNA-dependent protein kinases (de Murcia and Menissier de Murcia 1994).…”

Conservation of Sox4 gene structure and expression during chicken embryogenesis

“…It is expressed in salivary adenoid cystic carcinoma cells (Frierson et al, 2002) and medulloblastomas (Lee et al, 2002) and upregulated during apoptosis induced by protaglandins in hepatocellular carcinoma cells (Ahn et al, 1999). It is upregulated when human marrow stromal cells are induced to differentiate into osteoblasts by BMP-2 (Locklin et al, 2001), and is induced by perinatal asphyxia in rats (Lubec et al, 2002). Thus, Sox4 appears to have functions in a wide variety of developmental, physiological, and pathological processes.…”

Antenatal Maternal Long-Term Hypoxia: Acclimatization Responses with Altered Gene Expression in Ovine Fetal Carotid Arteries

“…These included brain ribonucleas (BRN-2), which has been shown to be downregulated in perinatal asphyxia in rat brain [52]. We also observed significant reduction in arachndonate 5-lipoxygenase-activating protein (ALOX5AP).…”