17beta-estradiol attenuates hyperoxia-induced apoptosis in mouse C8-D1A cell line.

In premature infants, oxygen free radicals generated following neonatal resuscitation are associated with subsequent diseases such as retinopathy of prematurity and bronchopulmonary dysplasia. Recent studies in brain tissue samples have shown that nonphysiologic oxygen levels play a key role in induction of apoptosis in the developing brain. Estrogen is a well-established agent in neuroprotection and, therefore, is thought to be neuroprotective even in the premature brain. Astrocytes appear to have a critical role in protection and survival of neurons in the brain. As one of the glial cell types, they have a great potential for possible involvement in the mediation of estrogen neuroprotective effects. The aim of our study was to analyze whether astrocytes in cell cultures are damaged by hyperoxia and whether 17beta-estradiol (E2) can protect them against apoptosis. Additionally, we investigated the mechanism of the protection by E2, hypothesizing that it is mediated through extracellular signal-regulated kinase (ERK1/2). Cells underwent eightfold more apoptosis when cultivated in hyperoxia compared with normoxia. Addition of E2 reduced apoptosis in hyperoxia by more than 50%. Levels of ERK1/2 and phosphorylated ERK1/2 were increased after hyperoxia compared with normoxia. Preincubation with E2 prior to exposure to hyperoxia resulted in decreased levels of ERK1/2 and pERK1/2. Hyperoxia induces apoptosis in C8-D1A cells, and E2 seems to be a protecting factor for astrocytes in hyperoxia. This effect is not mediated through up-regulation of pERK1/2.

Fetal akinesia caused by a novel actin filament aggregate myopathy skeletal muscle actin gene (ACTA1) mutation.

We report a female newborn, diagnosed with fetal akinesia in utero, who died one hour after birth. Post-mortem muscle biopsy demonstrated actin-filament myopathy based on immunolabelling for sarcomeric actin, and large areas of filaments, without rod formation, ultrastructurally. Analysis of DNA extracted from the muscle disclosed a novel de novo heterozygous c.44G>A, GGC>GAC, 'p.Gly15Asp' mutation in the ACTA1 gene. Analysis of the location of the mutated amino-acid in the actin molecule suggests the mutation most likely causes abnormal nucleotide binding, and consequent pathological actin polymerization. This case emphasizes the association of fetal akinesia with actin-filament myopathy.