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BackgroundThe aim of this work was to investigate the mechanisms by which chronic malnutrition (CM) affects vas deferens function, leading to compromised reproductive capacity. Previous studies have shown that maternal malnutrition affects the reproductive tracts of adult male offspring. However, little is known about the effects of CM, a widespread life-long condition that persists from conception throughout growth to adult life.Methodology/Principal FindingsYoung adult male rats, which were chronically malnourished from weaning, presented decreased total and haploid cells in the vas deferens, hypertrophy of the muscle layer in the epididymal portion of the vas deferens and intense atrophy of the muscular coat in its prostatic portion. At a molecular level, the vas deferens tissue of CM rats exhibited a huge rise in lipid peroxidation and protein carbonylation, evidence of an accentuated increase in local reactive oxygen species levels. The kinetics of plasma membrane Ca2+-ATPase activity and its kinase-mediated phosphorylation by PKA and PKC in the vas deferens revealed malnutrition-induced modifications in velocity, Ca2+ affinity and regulation of Ca2+ handling proteins. The severely crippled content of the 12-kDa FK506 binding protein, which controls passive Ca2+ release from the sarco(endo) plasmic reticulum, revealed another target of malnutrition related to intracellular Ca2+ handling, with a potential effect on forward propulsion of sperm cells. As a possible compensatory response, malnutrition led to enhanced sarco(endo) plasmic reticulum Ca2+-ATPase activity, possibly caused by stimulatory PKA-mediated phosphorylation.Conclusions/SignificanceThe functional correlates of these cellular and molecular hallmarks of chronic malnutrition on the vas deferens were an accentuated reduction in fertility and fecundity.

The molecular mechanisms involved in the Ang-(1-7) [angiotensin-(1-7)] effect on sodium renal excretion remain to be determined. In a previous study, we showed that Ang-(1-7) has a biphasic effect on the proximal tubule Na+-ATPase activity, with the stimulatory effect mediated by the AT1 receptor. In the present study, we investigated the molecular mechanisms involved in the inhibition of the Na+-ATPase by Ang-(1-7). All experiments were carried out in the presence of 0.1 nM losartan to block the AT1 receptor-mediated stimulation. In this condition, Ang-(1-7) at 0.1 nM inhibited the Na+-ATPase activity of the proximal tubule by 54%. This effect was reversed by 10 nM PD123319, a specific antagonist of the AT2 receptor, and by 1 muM GDP[beta-S] (guanosine 5'-[beta-thio]diphosphate), an inhibitor of G protein. Ang-(1-7) at 0.1 M induced [35S]GTP[S] (guanosine 5'-[gamma-[35S]thio]triphosphate) binding and 1 mug/ml pertussis toxin, an inhibitor of G(i/o) protein, reversed the Ang-(1-7) effect. Furthermore, it was observed that the inhibitory effect of Ang-(1-7) on the Na+-ATPase activity was completely reversed by 0.1 microM LY83583, an inhibitor of guanylate cyclase, and by 2 muM KT5823, a PKG (protein kinase G) inhibitor, and was mimicked by 10 nM d-cGMP (dibutyryl cGMP). Ang-(1-7) increased the PKG activity by 152% and this effect was abolished by 10 nM PD123319 and 0.1 microM LY83583. Taken together, these data indicate that Ang-(1-7) inhibits the proximal tubule Na+-ATPase by interaction with the AT2 receptor that subsequently activates the G(i/o) protein/cGMP/PKG pathway.

Background:Chrysophyllum pruniforme of family sapotaceae is a plant used in traditional medicine in Gabon.Materials and Methods:In this study, C. pruniforme barks were subjected to phytochemical screening and cytotoxicity investigations. Different concentrations of aqueous and total phenolic extract were tested on mice and on human erythrocytes.Results:Phytochemical screening of C. pruniforme barks revealed the presence of flavonoids, saponins, and tannins, reducing sugars, polyphenols and traces of anthraquinones. When tested in vitro, aqueous and the phenolic extracts showed hemolytic activities on human erythrocytes with phenolic compounds being more cytotoxic than aqueous extracts. In vivo study of toxicity, allowed to determine the LD50 at 90 mg/kg for the doses of 50, 150 and 250 mg/kg of body weight.Conclusion:These data indicate in one hand that C. pruniforme is rich in phenolic compounds and that the aqueous and total phenolic extracts could be considered as toxic for mice and maybe potentially toxic to humans in the other hand.

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Atividade inadequada do sistema renina-angiotensina-aldosterona local durante período de alta ingestão de sal: impacto sobre o eixo cardiorrenal Apesar de haver uma concordância geral sobre a necessidade de redução na ingestão de sal como questão de saúde publica, o mecanismo pelo qual a alta ingesta de sal deflagra efeitos patológicos sobre o eixo cardiorrenal não está ainda completamente elucidado. Cada vez mais evidencias indicam que o sistema renina-angiotensinaaldosterona (S-RAA) seja o principal alvo da alta ingesta de Na + . Uma ativação inadequada do S-RAA tecidual pode causar hipertensão e dano ao órgão. Nós revisamos o impacto da dieta com alto teor de sódio sobre o eixo cardiorrenal, destacando as vias moleculares que causam a lesão. Também fizemos uma avaliação de recentes estudos observacionais relacionados às consequên-cias do acúmulo de Na + não osmoticamente ativo, quebrando assim o paradigma de que a alta ingestão de sódio necessariamente aumenta a concentração sérica de Na + , assim promovendo a retenção de água. ResumoPalavras-chave: Renina; Angiotensina II; Sódio na Dieta; Rim; Coração.Although there is a general agreement on the recommendation for reduced salt intake as a public health issue, the mechanism by which high salt intake triggers pathological effects on the cardio--renal axis is not completely understood. Emerging evidence indicates that the renin-angiotensin-aldosterone system (RAAS) is the main target of high Na + intake. An inappropriate activation of tissue RAAS may lead to hypertension and organ damage. We reviewed the impact of high salt intake on the RAAS on the cardio-renal axis highlighting the molecular pathways that leads to injury effects. We also provide an assessment of recent observational studies related to the consequences of non-osmotically active Na + accumulation, breaking the paradigm that high salt intake necessarily increases plasma Na + concentration promoting water retention AbstRAct

Angiotensin II (Ang II) stimulates the proximal tubule Na(+)-ATPase through the AT(1) receptor/phosphoinositide phospholipase Cbeta (PI-PLCbeta)/protein kinase C (PKC) pathway. However, this pathway alone does not explain the sustained effect of Ang II on Na(+)-ATPase activity for 30 min. The aim of the present work was to elucidate the molecular mechanisms involved in the sustained effect of Ang II on Na(+)-ATPase activity. Ang II induced fast and correlated activation of Na(+)-ATPase and PKC activities with the maximal effect (115%) observed at 1 min and sustained for 30 min, indicating a pivotal role of PKC in the modulation of Na(+)-ATPase by Ang II. We observed that the sustained activation of PKC by Ang II depended on the sequential activation of phospholipase D and Ca(2+)-insensitive phospholipase A(2), forming phosphatidic acid and lysophosphatidic acid, respectively. The results indicate that PKC could be the final target and an integrator molecule of different signaling pathways triggered by Ang II, which could explain the sustained activation of Na(+)-ATPase by Ang II.

A new steroidal saponin, 3-{(O-6-deoxy-α-ʟ-mannopyranosyl-(1→4)-O-β-ᴅ-glucopyranosyl-( 1→3)-O-[O-β-ᴅ-glucopyranosyl-(1→3)-β-ᴅ-glucopyranosyl-(1→2)]-O-β-ᴅ-glucopyranosyl-( 1→4)-β-ᴅ-galactopyranosyl)oxy}-6-hydroxy-(3β,5α,6α,25R)-spirostan-12-one, was isolated from Agave brittoniana Trel. The structure was determined by extensive NMR spectroscopy studies and chemical conversions. Its effects on the Na+-ATPase and (Na++K+)-ATPase activities of the proximal tubule from pig kidney were evaluated. It was observed that this steroidal saponin exerts a biphasic effect on the Na+-ATPase activity. It is concluded that the effect of the aqueous extract as a diuretic is due, at least in part, to the action of saponin on the ouabain-insensitive Na+-ATPase.