Epigenetic Regulatory Effect of Exercise on Glutathione Peroxidase 1 Expression in the Skeletal Muscle of Severely Dyslipidemic Mice

Exercise is an effective approach for primary and secondary prevention of cardiovascular diseases (CVD) and loss of muscular mass and function. Its benefits are widely documented but incompletely characterized. It has been reported that exercise can induce changes in the expression of antioxidant enzymes including Sod2, Trx1, Prdx3 and Gpx1 and limits the rise in oxidative stress commonly associated with CVD. These enzymes can be subjected to epigenetic regulation, such as DNA methylation, in response to environmental cues. The aim of our study was to determine whether in the early stages of atherogenesis, in young severely dyslipidemic mice lacking LDL receptors and overexpressing human ApoB100 (LDLR^-/-; hApoB^+/+), exercise regulates differentially the expression of antioxidant enzymes by DNA methylation in the skeletal muscles that consume high levels of oxygen and thus generate high levels of reactive oxygen species. Expression of Sod2, Txr1, Prdx3 and Gpx1 was altered by 3 months of exercise and/or severe dyslipidemia in 6-mo dyslipidemic mice. Of these genes, only Gpx1 exhibited changes in DNA methylation associated with dyslipidemia and exercise: we observed both increased DNA methylation with dyslipidemia and a transient decrease in DNA methylation with exercise. These epigenetic alterations are found in the second exon of the Gpx1 gene and occur alongside with inverse changes in mRNA expression. Inhibition of expression by methylation of this specific locus was confirmed in vitro. In conclusion, Gpx1 expression in the mouse skeletal muscle can be altered by both exercise and dyslipidemia through changes in DNA methylation, leading to a fine regulation of free radical metabolism.     

The role of posture on the changes in plasma atrial natriuretic factor and arginine vasopressin levels during immersion

In seven healthy male volunteers we investigated changes in plasma atrial natriuretic factor [( ANF]), arginine vasopressin [( AVP]) and plasma volume (PV) during supine immersion. Twenty minutes head-out water immersion in a supine position in a thermo-neutral water bath attenuated the increase in PV induced by 20 min in a supine position in air, but increased the mean plasma [ANF] from 32.0 pg.ml-1, SEM 5.1 to 53.3 pg.ml-1, SEM 3.6 and decreased the mean plasma [AVP] from 1.4 pg.ml-1, SEM 0.1 to 0.9 pg.ml-1, SEM 0.04. Simultaneously, diuresis and natriuresis increased markedly. During a 20-min control period in the supine posture without immersion, PV, plasma [ANF] and [AVP] remained unaffected while diuresis and natriuresis did not increase to the same extent. These data suggest that an increase in the central blood volume induced by a weak external hydrostatic pressure during supine immersion triggered the changes in plasma [ANF] and [AVP] and that the increase was probably due to a shift of blood volume from peripheral to central vessels. The changes in plasma [ANF] contributed to the changes in natriuresis.     

Assignment of the human CD9 gene to chromosome 12 (region P13) by use of human specific DNA probes

Summary We have used human specific DNA probes and somatic hybrid cell analysis to localize the human CD 9 gene to chromosome 12 (region p13).     

Sapindus sonlaensis (Sapindaceae), a new species from Vietnam

A rare new species of Sapindus from Vietnam, Sapindus sonlaensis, is described, illustrated, and compared to similar species.     

Purification and primary structure of pro-aldosterone secretion inhibitory factor from bovine adrenal chromaffin cells

This report documents the purification and the complete primary structure of bovine aldosterone secretion inhibitory factor precursor (pro-ASIF). ASIF-(1-103) contains at position 69-103 of its carboxy-terminal end the formely identified 35-amino acid biologically active form, hence confirming the endogenous character of ASIF in the adrenal medulla. Compared to atrial natriuretic factor (ANF)-related peptide precursors, bovine ASIF displays 65% homology at the carboxy-terminal while the remaining amino-terminal part shows much more variability. Bovine pro-ASIF exhibits 73% homology with porcine pro-brain natriuretic peptide (BNP), a situation reminiscent of the relationship of pro-ANF in various species. When ANF- and BNP-related COOH-termini of bovine, porcine, human, rat, and chicken are compared, it appears that bovine ASIF and porcine BNP are closely related and belong to the same family which however appears to be much more heterogenous than the ANF-related family. These results strongly suggest that bovine ASIF is encoded by a precursor gene similar to the gene of BNP but different from the one encoding ANF.     

Computational analysis of pediatric ventricular assist device implantation to decrease cerebral particulate embolization

Stroke is the most devastating complication after ventricular assist device (VAD) implantation with a 19% incidence and 65% mortality in the pediatric population. Current pediatric VAD technology and anticoagulation strategies alone are suboptimal. VAD implantation assisted by computational methods (CFD) may contribute reducing the risk of cerebral embolization. Representative three-dimensional aortic arch models of an infant and a child were generated. An 8 mm VAD outflow-graft (VAD-OG) anastomosed to the aorta was rendered and CFD was applied to study blood flow patterns. Particle tracks, originating in the VAD, were computed with a Lagrangian phase model and the percentage of particles entering the cerebral vessels was calculated. Eight implantation configurations (infant = 5 and child = 3) and 5 particle sizes (0.5, 1, 2, 3, and 4 mm) were considered. For the infant model, percentage of particles entering the cerebral vessels ranged from 15% for a VAD-OG anastomosed at 90° to the aorta, to 31% for 30° VAD-OG anastomosis (overall percentages: X² = 10,852, p < 0.0001). For the child model, cerebral embolization ranged from 9% for the 30° VAD-OG anastomosis to 15% for the 60° anastomosis (overall percentages: χ² = 10,323, p < 0.0001). Using detailed CFD calculations, we demonstrate that the risk of stroke depends significantly on the VAD implantation geometry. In turn, the risk probably depends on patient-specific anatomy. CFD can be used to optimize VAD implantation geometry to minimize stroke risk.     

Early Deficits in Glycolysis Are Specific to Striatal Neurons from a Rat Model of Huntington Disease

In Huntington disease (HD), there is increasing evidence for a link between mutant huntingtin expression, mitochondrial dysfunction, energetic deficits and neurodegeneration but the precise nature, causes and order of these events remain to be determined. In this work, our objective was to evaluate mitochondrial respiratory function in intact, non-permeabilized, neurons derived from a transgenic rat model for HD compared to their wild type littermates by measuring oxygen consumption rates and extracellular acidification rates. Although HD striatal neurons had similar respiratory capacity as those from their wild-type littermates when they were incubated in rich medium containing a supra-physiological glucose concentration (25 mM), pyruvate and amino acids, respiratory defects emerged when cells were incubated in media containing only a physiological cerebral level of glucose (2.5 mM). According to the concept that glucose is not the sole substrate used by the brain for neuronal energy production, we provide evidence that primary neurons can use lactate as well as pyruvate to fuel the mitochondrial respiratory chain. In contrast to glucose, we found no major deficits in HD striatal neurons’ capacity to use pyruvate as a respiratory substrate compared to wild type littermates. Additionally, we used extracellular acidification rates to confirm a reduction in anaerobic glycolysis in the same cells. Interestingly, the metabolic disturbances observed in striatal neurons were not seen in primary cortical neurons, a brain region affected in later stages of HD. In conclusion, our results argue for a dysfunction in glycolysis, which might precede any defects in the respiratory chain itself, and these are early events in the onset of disease.