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Biomedical subjects

F Alba

Publications and source records attributed to F Alba.

At least 19 recordsLinked to original sources

Angiotensinase activity in hypothalamus and pituitary of hypothyroid, euthyroid and hyperthyroid adult male rats.

A local renin-angiotensin system (RAS) that may be involved in their regulatory functions has been identified in hypothalamus and pituitary. Altered thyroid status induces modifications in the secretory function of hypothalamus and pituitary. However, few studies have analyzed the role of the RAS in hypothalamus and, to our knowledge, there is no data on the pituitary RAS during thyroid dysfunction. In the present study, angiotensinase activities (glutamyl, aspartyl and alanyl aminopeptidase: GluAP, AspAP and AlaAP, respectively) were studied in hypothalamus and in the anterior and posterior lobes of pituitary of euthyroid, hypothyroid and hyperthyroid adult male rats. In the anterior pituitary, compared with euthyroid and hyperthyroid rats, hypothyroid animals showed a highly significant increase of GluAP and AspAP activities; the percentage increase in GluAP was markedly higher than the percentage increase in AspAP. This suggests an increased metabolism of angiotensin (Ang) I and Ang II to des-Asp 1-Ang I and Ang III, respectively. We also observed an increase of Ang III-degrading activity (AlaAP) in the hypothalamus of hyperthyroid rats in soluble fraction. Increased Ang I and Ang II metabolism in the anterior pituitary of hypothyroid rats and increased metabolism of Ang III in the hypothalamus of hyperthyroid animals may be related to alterations in the secretory function of hypothalamus and pituitary in these thyroid dysfunctions.

Animals↗

Effects of dehydration on renal aminopeptidase activities in adult male and female rats.

Aminopeptidases (APs) are important regulators of peptides directly involved in water homeostasis such as angiotensins (Ang) and vasopressin (AVP). Sex differences in water balance and differences in the effects of gonadal steroids on osmotic stimulation of vasopressin secretion have been reported. Since sex steroids may be involved, the gonadotropin response to osmotic stimuli may be different between males and females. The purpose of this study was to determine the behavior of angiotensinases, vasopressin-degrading activity and gonadotropin-releasing hormone (GnRH)-degrading activity in the cortex and medulla of the kidney of dehydrated male and female rats. In the renal cortex, our results demonstrated an increase in Ang III-degrading activity in dehydrated males but not in females. This response may lead to an increased formation of Ang IV. This occurs with an increase in AspAP activity (which metabolizes Ang I to des-Asp(1)-Ang I), with no changes in Ang II-degrading activity and also with increased levels of AVP-degrading activity in dehydrated animals. These results may suggest an increased cortical blood flow due to enhanced formation of Ang IV together with reduced availability of the vasoconstrictor agents Ang II and AVP in the renal cortex of dehydrated males. The results obtained in the renal medulla suggest the inhibition of the metabolism of Ang I to des-Asp(1)-Ang I, together with a reduced metabolism of Ang II and AVP in dehydrated males but not in females. These results suggest a prolonged action of Ang II and AVP, which could stimulate sodium and water reabsorption in the medulla of dehydrated males. Changes in APs after dehydration occur preferentially in males, which may explain in part the reported sex differences in water homeostasis. The present results suggest a physiologically relevant role for AP activities in water homeostasis.

Aging↗

Aminopeptidase activities after water deprivation in male and female rats.

Aminopeptidases (APs) play a major role in the metabolism of circulating and local peptides, such as angiotensins and vasopressin, substances involved in the control of blood pressure and water balance. In the present work, we studied the influence of dehydration on angiotensinases and vasopressin-degrading activity. Since sex differences may exist in the regulation of water balance by angiotensin II and differential sexual steroid modulation of vasopressin secretion, in response to osmotic stimulation have been reported, gonadotropin releasing hormone (GnRH)-degrading activity was also analysed in serum, neurohypophysis and adrenal glands of male and female rats. Our results did not suggest sex differences in the response to changes in osmolality. GnRH-degrading activity decreased in serum of dehydrated males and females, which suggests a longer action of the peptide under these conditions. In neurohypophysis, there was an increase in the activity of aminopeptidase A (APA), the enzyme responsible for the metabolism of angiotensin II to angiotensin III. This occurs with a decrease in alanyl aminopeptidase activity, which would lead to a prolonged action of angiotensin III by reduction of its metabolism. In adrenals of dehydrated animals, the results would imply a high degree of metabolism of angiotensin III and vasopressin.

Adrenal Glands↗

Angiotensinase activity in mice fed an olive oil-supplemented diet.

We evaluated the influence of a diet supplemented with olive oil (20% by weight) (OO) on the activity of glutamyl aminopeptidase (GluAP) and aspartyl aminopeptidase (AspAP), which are involved in angiotensin metabolism. Serum concentrations of total cholesterol and fatty acids were also measured. Animals fed on the OO diet gained significantly more weight than did controls from the second week until the end of the feeding period. Serum total cholesterol concentration was significantly higher in the OO group than in control mice. Total monounsaturated fatty acids increased in OO-fed animals, but total saturated fatty acids decreased. No differences between the two groups were observed for total polyunsaturated fatty acids. Serum from animals fed on the OO diet contained significantly lower proportions of myristic, pentadecanoic, palmitic, palmitoleic, vaccenic, alpha-linolenic, gamma-linolenic, and 11,14-eicosadienoic acids than did serum from control animals. In contrast, the OO group had higher levels of oleic, stearic, and gondoic acids. GluAP activity decreased significantly in the serum of OO-fed animals. In these animals soluble AspAP activity was significantly higher in the testis, and significantly lower in the lung and adrenal, in comparison to controls. Membrane-bound AspAP activity was higher in the testis and atrium, and lower in lung, in the OO group. Soluble GluAP activity was significantly lower in the testis of OO-fed animals. Membrane-bound GluAP activity did not differ between the two groups in any of the tissues analyzed. Serum AspAP and GluAP activities correlated negatively with palmitoleic and vaccenic acid respectively in the OO group. However, no significant correlations were found in the control group. These results may reflect functional changes in the renin-angiotensin system in the serum, adrenal, testis, lung and atrium after feeding with a diet enriched in olive oil.

Aminopeptidases↗

Environmental light-darkness conditions induce changes in brain and peripheral pyroglutamyl-peptidase I activity.

To evaluate the influence of light and darkness on brain pyroglutamyl-peptidase I (pGluPI) activity, four experimental groups of rats were compared at the same time-point (10.00 h). Two groups were designed with a standard 12-12 h light-dark cycle: In group A, the lights were on from 7.00 h to 19.00 h, and the experiment was done under light conditions; in group B, the lights were on from 19.00 h to 7.00 h, and the experiment was done under darkness conditions. Two additional groups were designed with nonstandard light-dark conditions: In group C, the animals were subjected to constant light, and the experiment was done under light conditions. In group D, animals were subjected to constant darkness, and the experiment was done under darkness conditions. Light (vs darkness) and standard (vs nonstandard) conditions produced significant changes on pGluPI activity in specific structures; the data suggested that endogenous substrates of pGluPI such as thyrotropin-releasing hormone and gonadotropin-releasing hormone, might be modified in parallel. There was left predominance in the retina under light conditions on a standard schedule (group A). The regional pattern of distribution of activity was similar in groups on a standard schedule (A vs B) and in groups tested under constant light-dark conditions (C vs D). However, this pattern differed between groups subjected to standard vs constant light-dark conditions (A and B vs C and D). These results support an influence of environmental light and darkness on pGluPI activity, which may reflect concomitant changes in its susceptible substrates and consequently in their functions.

Animals↗

Effect of valsartan on angiotensin II- and vasopressin-degrading activities in the kidney of normotensive and hypertensive rats.

Valsartan, a selective antagonist of angiotensin II at the AT(1) receptor subtype, is an efficacious, orally active, blood pressure-lowering agent used in hypertensive patients. Given that aminopeptidases (APs) play a major role in the metabolism of local peptides involved in blood pressure control, studying them helped us to understand cardiovascular control. We studied the effect of valsartan on angiotensin II- (GluAP) and vasopressin- (CysAP) degrading activities in the kidney in the rat model of renovascular hypertension, Goldblatt two-kidney one-clip. GluAP and CysAP in renal cortex and medulla exhibited different responses to hypertension and valsartan treatment. In the renal cortex, GluAP decreased in clipped and non-clipped kidneys of hypertensive animals. However, while hypertension did not affect GluAP in the clipped kidney medulla, the non-clipped kidney exhibited an increase in soluble and a decrease in membrane-bound activity. Valsartan decreased soluble GluAP in the medulla of normotensive and hypertensive animals. In the renal cortex, CysAP activity was mainly downregulated following hypertension. Valsartan decreased soluble CysAP activity in sham-operated, but not in hypertensive animals. The renal medulla showed a significant valsartan-related decreased activity in clipped and non-clipped kidneys of both sham-operated and hypertensive animals. These results suggest a functional relationship between the AT(1) receptor and vasopressin-degrading activity.

Aminopeptidases↗

Serum aminopeptidase A activity of mice is related to dietary fat saturation.

A high intake of monounsaturated fat has been proposed to be a dietary factor that can decrease the incidence of cardiovascular disease and hypertension. In addition, increasing dietary fat saturation has been shown to increase plasma total cholesterol and elevate systolic and diastolic blood pressures. We demonstrated previously that cholesterol selectively increases in vitro aminopeptidase A activity, which is related to angiotensin metabolism. In this study, we investigated the effect of different degrees of dietary fatty acid saturation on serum aminopeptidase activities in vivo. Serum total cholesterol concentrations were also measured. Five groups of male Balb/C mice were fed for 10 wk diets containing 2.4 g/100 g of sunflower oil, fish oil, olive oil, lard or coconut oil. We measured alanyl-, arginyl-, cystinyl-, pyroglutamyl-, aspartyl- and glutamyl-specific aminopeptidase activities using arylamides as substrates. Serum total cholesterol levels were higher in mice fed diets containing saturated oils (lard and coconut) than in those consuming sunflower oil, which is unsaturated. Two of the serum aminopeptidase A activities (aspartyl and glutamyl aminopeptidase) increased progressively with the degree of saturation of the dietary fatty acids; activities were significantly greater in mice fed coconut oil than in those fed sunflower or fish oil. Therefore, the substrates hydrolyzed by this activity as well as their functions may be similarly affected. These results may have some implication for the treatment of cardiovascular disease.

Aminopeptidases↗

The effect of meteorological factors on the daily variation of airborne fungal spores in Granada (southern Spain).

A study was made of the link between climatic factors and the daily content of certain fungal spores in the atmosphere of the city of Granada in 1994. Sampling was carried out with a Burkard 7-day-recording spore trap. The spores analysed corresponded to the taxa Alternaria, Ustilago and Cladosporium, with two morphologically different spore types in the latter genus, cladosporioides and herbarum. These spores were selected both for their allergenic capacity and for the high level of their presence in the atmosphere, particularly during the spring and autumn. The spores of Cladosporium were the most abundant (93.82% of the total spores identified). The Spearman correlation coefficients between the spore concentrations studied and the meteorological parameters show different indices depending on the taxon being analysed. Alternaria and Cladosporium are significantly correlated with temperature and hours of sunlight, while Ustilago shows positive correlation indices with relative humidity and negative indices with wind speed.

Air Microbiology↗

Oral administration of losartan influences aminopeptidase activity in the frontal cortex.

Although there is a brain renin-angiotensin system, its mechanisms of control are not fully understood. We studied the effect of oral administration of the AT(1) receptor antagonist losartan on brain aminopeptidase (AP) activity, which plays a major role in neuropeptide metabolism. Six AP activities, related and non-related with the angiotensin (Ang) metabolism, were measured in their soluble and membrane-bound forms in the frontal cortex of control animals and rats treated with losartan, chronically administered via the drinking water. The results demonstrate that soluble pGluAP and membrane-bound AspAP and GluAP increased significantly in losartan-treated animals, indicating that the blockade of the AT(1) receptor stimulates the activity of AP involved in the Ang metabolism. Moreover, the blockade of the AT(1) receptor induces changes not only in the brain angiotensin metabolism, but probably also in that of other neuropeptides.

Administration, Oral↗

Comparative distribution of glutamyl and aspartyl aminopeptidase activities in mouse organs.

To evaluate the functional role of glutamyl and aspartyl aminopeptidases, their soluble and membrane-bound activities were measured simultaneously in several tissues of normal mice using arylamide derivatives as substrates. Although the soluble aspartyl aminopeptidase activity showed its highest levels in the testicle, the rest of the activities presented their highest levels in the kidney. Different patterns of distribution were observed for glutamyl and aspartyl aminopeptidase activities and also for soluble and membrane-bound aspartyl aminopeptidase activities. However no major differences were observed between soluble and membrane-bound glutamyl aminopeptidase activities. This unequal distribution suggests that the use of arylamide derivatives as substrates is a sensitive method that distinguishes between these enzymatic activities. The results also suggest different functions for soluble and membrane-bound aspartyl aminopeptidase activities, and for glutamyl and aspartyl aminopeptidase activities.

Adrenal Glands↗

HLA-DRB1*01 and DRB1*04 alleles in Sardinian rheumatoid arthritis patients.

In Sardinia, like in other Caucasoid populations, rheumatoid arthritis (RA) is significantly associated with HLA-DR4 and DR1 antigens. To discover which DR4 and DR1 alleles were associated with the disease we selected 22 Sardinian patients affected by RA. Fifty DR4+ and 28 DR1+ healthy individuals coming from the same geographical area were used as controls. In the Sardinian patients only two DRB1*04 alleles were observed: DRB1*0405 in 11 and DRB1*0403 in three patients. The DRB1*0102 allele was observed in two patients and DRB1*0101 in six patients. Hereditary predisposition to RA in Sardinia therefore seems to be almost exclusively associated with the DRB1*0405 and DRB1*0101 alleles which share the 67LLEQRRAA74-85VG86 epitope in the peptide binding groove.

Alleles↗

Lateralization of aminopeptidase A activity in substantia nigra, striatum and frontal cortex of rats.

Several brain aminopeptidase activities have been reported to be asymmetrical, but no direct correlation with lateralized functions has been proposed. Cholecystokinin (CCK) coexists with dopamine (DA) in the nigrostriatal system, which is involved in lateralized motor behaviors. Because aminopeptidase A activity is probably responsible for the hydrolysis of CCK, we studied the left-right distribution of glutamate- (GluAP) and aspartate-aminopeptidase (AspAP) activities in their soluble (Sol) and membrane-bound (M-B) forms in the substantia nigra, striatum and cortex of rats. Although there was a highly significant predominance of the left side in the substantia nigra and striatum for Sol GluAP and M-B AspAP respectively, in the frontal cortex predominance was on the right side for M-B AspAP. These results suggest a relationship between aminopeptidase A activity and lateralized nigro-striato-cortical functions involving CCK.

Aminopeptidases↗

Changes in membrane-bound leucine aminopeptidase activity during maturation and ageing of brain.

Aminopeptidases are believed to be enzymes that regulate the activity of various neuropeptides. However, their physiological role, as well as their mechanisms of regulation, are not well understood. To analyze a part of the regulatory mechanisms that control the activity of these enzymes, the subcellular distribution of membrane-bound leucyl aminopeptidase activity was studied in rat brain during development and ageing. Except in fetuses, the enzymic activity was greatest in the microsomal fraction in all ages tested. Except in microsomal and myelin fractions, compared with fetuses, leucyl aminopeptidase activity showed a decrease in 1-week-old rats and a subsequent increase to adult levels in 1-month-old rats. This profile differed in the microsomal fraction, where the activity increased steadily up to 1-month-old rats. After this age, the activity decreased progressively in 5-month and 24-month-old rats. These results may reflect changes in the functional status of the susceptible substrates during development and ageing.

Aging↗

Aminopeptidase activities in breast cancer tissue.

BACKGROUND: Endopeptidases such as cathepsins help determine the prognosis of breast cancer (BC). However, little information is available about the role in BC of aminopeptidases (APs), which have been implicated in the metabolism of several local hormonal factors. METHODS: Using aminoacyl-beta-naphthylamides as substrates, we measured fluorometrically alanyl-AP, arginyl-AP, cystinyl-AP, glutamyl-AP, aspartyl-AP, and pyroglutamyl-AP activities in their soluble and membrane-bound forms in surgically removed BC tissue from which we separated samples of neoplastic, adjacent tumoral, and unaffected surrounding tissue. RESULTS: Compared with unaffected tissue, neoplastic tissue had significantly higher activities of soluble alanyl-AP (553.9 +/- 82.8 vs 1615.2 +/- 183.0 pmol/mg protein; P <0.001), arginyl-AP (372.4 +/- 56.6 vs 1027.2 +/- 143.5 pmol/mg protein; P <0.001), and cystinyl-AP (74.8 +/- 10.0 vs 282.9 +/- 37.2 pmol/mg protein; P <0.001), and of membrane-bound arginyl-AP (457.7 +/- 97.9 vs 886.6 +/- 140.0 pmol/mg protein; P <0.01). However, membrane-bound aspartyl-AP activity was significantly lower in neoplastic tissue (17.3 +/- 1.4 vs 9.2 +/- 1.2 pmol/mg protein; P <0.05) and pyroglutamyl-AP activity was significantly lower in neoplastic and adjacent tissues (12.8 +/- 0.9 vs 7.0 +/- 1. 2 and 8.0 +/- 1.3 pmol/mg protein; P <0.001 for both comparisons). CONCLUSIONS: The present results document changes in AP activities in BC tissue. These changes may reflect the functional status of the AP substrates, which can be selectively activated or inhibited locally in the affected tissue as a result of specific conditions brought about by the tumor.

Aminopeptidases↗

[Sertoli-Leydig tumor. Clinical case].

We report a 16 year old girl presenting with secondary amenorrhea, a history of voice coarsening, hirsutism and a body mass index of 35 kg/m2. Pelvic ultrasound and CT scans showed a retro uterine dense mass. She was operated and a left ovarian tumor was excised. Pathological examination disclosed a Sertoli-Leydig tumor.

Adolescent↗

Sex differences and age-related changes in human serum aminopeptidase A activity.

Given that aminopeptidase A is primarily responsible for cleaving aspartic acid and converting angiotensin II to angiotensin III, the purpose of the present study was to evaluate the activity of aminopeptidase A by determination of glutamate aminopeptidase activity (GluAP) and aspartate aminopeptidase activity (AspAP) (reported respectively as aminopeptidase A and angiotensinase A activities) in human serum during development and ageing, in an apparently healthy population of 139 male and 148 female subjects. To measure GluAP and AspAP we used glutamyl- and aspartyl-2-naphthylamide as substrates. Significant age-related increases were observed in GluAP activity in males and females and in AspAP activity in females. In males, there were no age-related differences in AspAP activity. A significant correlation was observed between age and GluAP activity in the population analysed as a whole or according to sex. No correlation was demonstrated between age and AspAP activity either in the whole population or according to sex. These results may reflect the evolution of the functional status of susceptible circulating substrates during development and ageing.

Adolescent↗

Sex differences and in vitro effects of steroids on serum aminopeptidase activities.

We studied the possible existence of physiological sex differences in serum aminopeptidase activities in mice, by evaluating the effect of gonadectomy and the in vitro response to the presence in the medium of cholesterol or steroid hormones. Alanyl- and glutamyl-aminopeptidase activities were measured in sera from male, female, orchiectomized and ovariectomized mice, incubated with substrate solutions, and compared with the same groups of serum incubated with substrate solutions including cholesterol, 17-beta-estradiol, testosterone, progesterone or hydrocortisone. Our results demonstrated highly significant sex differences, and an influence of cholesterol and steroid hormones on aminopeptidase activity. Depending on the nature of the aminopeptidase, these enzymes responded in different ways to the presence of these substances and also responded differently to gonadectomy. For alanyl-aminopeptidase activity, but not for glutamyl-aminopeptidase activity, there was a clear difference in response between males and females to incubation of the serum with steroid hormones.

Aminopeptidases↗

Activities of aminopeptidases in a rat saline model of volume hypertension.

Aminopeptidase activity plays a role in the metabolism of several peptides that could be involved in blood pressure control. This activity has been implicated in the pathogenesis of hypertension, essentially in spontaneously hypertensive rats. However, few studies have examined aminopeptidase activities in animal models other than genetic hypertension. To analyze the aminopeptidase response to the specific conditions of the reduced renal mass saline model of arterial hypertension, aminopeptidase A activity (glutamyl- and aspartyl-aminopeptidase), aminopeptidase M activity (alanyl-aminopeptidase), aminopeptidase B activity (arginyl-aminopeptidase), pyroglutamyl-aminopeptidase and cystinyl-aminopeptidase were measured in the neurohypophysis, in the adrenal gland and in serum of this model of hypertension. In the neurohypophysis, there was a significant increase of soluble cystinyl-, alanyl-, arginyl-, pyroglutamyl- and membrane-bound aspartyl-aminopeptidase activities in hypertensive animals. In the adrenal gland, soluble cystinyl-, alanyl-, arginyl- and pyroglutamyl-aminopeptidase activities were also higher in hypertensive rats than in normotensive controls. No differences were found in serum levels of aminopeptidase activities between both groups of animals. A highly significant positive correlation between the neurohypophysis and the adrenal gland was observed for soluble cystinyl- and alanyl-aminopeptidase activities in the model of hypertension, whereas no correlation was observed in normotensive rats. Our results suggest that aminopeptidase activities could be involved in the regulatory response to the reduced renal mass hypertension and also suggest a coordinate response between the adrenal gland and the neurohypophysis, to the specific metabolic conditions of this model of hypertension.

Adrenal Glands↗