Reduction of cardiac and renal dysfunction by new inhibitor of DPP4 in diabetic rats.

Background: Increased mortality due to type 2 diabetes mellitus (T2DM) has been associated with renal and/or cardiovascular dysfunction. Dipeptidyl dipeptidase-4 inhibitors (iDPP-4s) may exert cardioprotective effects through their pleiotropic actions via glucagon-like peptide 1-dependent mechanisms. In this study, the pharmacological profile of a new iDPP-4 (LASSBio-2124) was investigated in rats with cardiac and renal dysfunction induced by T2DM.

Long-term effect of a chronic low-protein multideficient diet on the heart: Hypertension and heart failure in chronically malnourished young adult rats.

Background: We investigated whether a chronic low-protein multideficient diet (BRD) from weaning turns on cardiovascular adaptive responses that could culminate in hypertension and heart failure.

Methods And Results: Systolic pressure (SP) and heart rate (HR) were determined in CTRL (normal diet) and BRD rats. Plasma albumin, plasma urea and urinary urea excretion decreased in BRD rats.

Rats undernourished in utero have altered Ca2+ signaling and reduced fertility in adulthood.

Epidemiological and animal studies have shown that placental undernutrition impairs reproduction in adult offspring, but the underlying molecular mechanisms within the male genital tract remain unknown. Due to its special physiological characteristics in transport and the modulation of the environment to which its luminal content is exposed, we hypothesized that the vas deferens would be a highly sensitive target. The goals were to investigate whether intrauterine malnutrition affects molecular mechanisms related to Ca(2+)- and oxidative stress-modulated processes and causes structural alterations in the adult rat vas deferens that could attenuate fecundity and fertility.

Different effects of myotoxins bothropstoxin-I and II from Bothrops snake venom on cation transport ATPases from murine fast twitch skeletal muscle.

Bothrops jararacussu venom drastically decreases sarcoplasmic Ca(2+)-ATPase (SERCA) protein expression in vivo and inhibits its activity in vitro, in contrast to a slight increase of Na(+)/K(+)-ATPase expression in murine EDL. We investigated the effect of myotoxins bothropstoxin-I and/or -II (BthTX-I, BthTX-II and BthTX-I+II) on this model. No changes were seen in SERCA1, SERCA2 and Na(+)/K(+)-ATPase α1 protein expression as well as (2+)Ca-ATPase activity, but BthTX-II (1 μg/g) reduced Na(+)/K(+)-ATPase α2 expression by 50% one day after perimuscular injection.

Undernutrition affects cell survival, oxidative stress, Ca2+ handling and signaling pathways in vas deferens, crippling reproductive capacity.

Background: The 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.

Mechanisms associated to impaired activity of cardiac P-type ATPases in endothelial nitric oxide synthase knockout mice.

The effect of long-lasting in vivo restriction of nitric oxide (NO) bioavailability on cardiac and renal P-type ATPases critical for intracellular ion homeostasis is controversial. Previous work has shown in eNOS knockout (eNOS(-/-)) mice hearts that Na(+)/K(+)- and Ca(2+)-ATPase activities were depressed but the underlying mechanisms are still unclear. The goal of this study was to characterize potential alterations responsible for impaired enzyme activity in eNOS(-/-) mice.

Effect of heparin treatment on the expression and activity of different ion-motive P-type ATPase isoforms from mouse extensor digitorum longus muscle during degeneration and regeneration after Bothrops jararacussu venom injection.

Ca(2+) ions are essential to myonecrosis, a serious complication of snake envenomation, and heparin seems to counteract this effect. We investigated the effect of local injection of Bothrops jararacussu venom in mouse fast-twitch extensor digitorum longus (EDL) muscle, without or with heparin, on functional/molecular alterations of two central proteins involved in intracellular Ca(2+) homeostasis, sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) and Na(+)/K(+)-ATPase. EDL-specific SERCA1 isoform expression dropped significantly just after venom administration (up to 60% compared to control EDL values at days 1 and 3; p<0.

Adaptive expression pattern of different proteins involved in cellular calcium homeostasis in denervated rat vas deferens.

The activity and protein expression of plasma membrane and sarco(endo)plasmic reticulum (Ca2+-Mg2+)ATPases and ryanodine receptors were investigated in surgically denervated rat vas deferens. The function of thapsigargin-sensitive but not thapsigargin-resistant (Ca2+-Mg2+)ATPase (from sarco(endo)plasmic reticulum and plasma membrane, respectively), evidenced by enzyme activity and Ca2+ uptake experiments, was significantly depressed by 30-50% when compared to innervated vas. Western blots showed that such reduction in sarco(endo)plasmic reticulum (Ca2+-Mg2+)ATPase performance was accompanied by a decrement of similar magnitude in sarco(endo)plasmic reticulum (Ca2+-Mg2+)ATPase type 2 protein expression, without any significant change in plasma membrane (Ca2+-Mg2+)ATPase expression.

Characterization of subcellular fractions and distribution profiles of transport components involved in Ca(2+) homeostasis in rat vas deferens.

Introduction: The sarcoplasmic reticulum present in eukaryotic cells contains Ca(2+) pumps (SERCA type) that accumulate Ca(2+) from the cytosol and Ca(2+) channels, such as ryanodine receptors and inositol 1,4,5-trisphosphate receptors, that release Ca(2+) from the lumen of this organelle. The use of a preparation rich in sarcoplasmic reticulum vesicles and poorly contaminated with plasmalemmal vesicles would be a prerequisite for studies of Ca(2+) efflux through ryanodine and inositol 1,4,5-trisphosphate receptors, so the present work was aimed to characterize the distribution profiles of various markers of sarcoplasmic reticulum and plasma membrane among fractions obtained from rat vas deferens.

Methods: Oxalate-dependent Ca(2+) uptake, thapsigargin-sensitive (Ca(2+)-Mg(2+)) ATPase activity and binding of [3H]ryanodine and [3H]inositol 1,4,5-trisphosphate were measured in the nuclear, mitochondrial, and microsomal fractions obtained by differential centrifugation of rat vas deferens homogenate.