Search PubMed⌕ Search

Biomedical subjects

F Raul

Publications and source records attributed to F Raul.

At least 55 records · Page 3Linked to original sources

Premature expression of sucrase-isomaltase triggered by corticoid-dependent changes in polyamine metabolism.

A possible link between the corticoid-elicited premature expression of intestinal sucrase-isomaltase (SI) and endogenous changes in polyamine metabolism was investigated in preweaned rats. Starvation at postnatal day 12 caused a precocious expression of SI mRNA and activity. A rapid upsurge of serum corticosterone was observed during the first hour of isolation, occurring in parallel with a transient enhancement of ornithine decarboxylase (ODC) expression and followed by an increase in mucosal polyamine content. Administration of the antiglucocorticoid RU-38486 completely prevented the starvation-evoked stimulation of ODC. The treatment of the sucklings with RU-38486 or with alpha-difluoromethylornithine (DFMO), a specific inhibitor of ODC, dramatically reduced the amount of SI mRNA. When exogenous hydrocortisone (HC) was administered to 12-day-old sucklings nourished by their dam, an important accumulation of ODC mRNA was observed in the intestinal mucosa 4 h after treatment. Sucklings receiving HC and treated concomitantly with either RU-38486 or DFMO exhibited a reduced amount of ODC mRNA and a dramatic decline in both SI mRNA and activity. Altogether these data support the view that the premature induction of SI expression is dependent on changes in ODC expression and polyamine metabolism that can be elicited either by endogenous changes or by exogenously administered glucocorticoids.

Animals↗

Beneficial effects of L-arginine on intestinal epithelial restitution after ischemic damage in rats.

The polyamines are involved in repair processes after intestinal ischemia. Arginine and ornithine, both precursors of polyamines were therefore expected to exert beneficial effects on mucosal barrier dysfunction. Arginine may also generate NO and there is support for the view that NO may be beneficial after an ischemic insult. Male Wistar rats were given, by gavage, isonitrogenous solutions of L-arginine (0.5 g/kg) or L-ornithine (0.7 g/kg) 17 and 2 h before ischemia. Controls received an isonitrogenous solution of casein hydrolysate (1 g/kg). Transient intestinal ischemia was produced in anesthetized rats by occluding the superior mesenteric artery for 90 min. Intestinal morphology, hydrolase activities, polyamine and cGMP contents, and cell proliferation rates were determined 4 h after reperfusion. Administration of arginine or ornithine did not prevent ischemic damage but accelerated morphological repair, enhanced cell proliferation, and polyamine content was observed. Arginine was significantly more effective than ornithine. Formation of cGMP was enhanced after arginine administration. NG-nitroarginine methylester, an inhibitor of NO synthase, prevented the arginine effects on mucosal repair. We conclude that arginine-derived NO is an important mediator in the restitution of intestinal mucosa by minimizing cell injury during reperfusion.

Aminopeptidases↗

Intestinal absorption of calcium in vivo is dependent on endogenous nitric oxide.

This study examines the role of nitric oxide (NO) in the regulation of calcium absorption in the small intestine. Calcium absorption was quantified by measuring 45Ca++ transport from lumen to blood in an intestinal segment (duodenum and 20 cm of the proximal jejunum) perfused by both intraluminal and vascular routes in anesthetized rats. When administered i.v. as bolus injections, NG-nitro-L-arginine methyl ester (L-NAME, 10 mg.kg-1), an inhibitor of NO biosynthesis, decreased calcium absorption with a concomitant increase in blood pressure and a decrease in mesenteric blood flow. Conversely, the nitrovasodilators 3-morpholinosydnonimine (2 mg.kg-1) and S-nitroso-N-acetylpenicillamine (10 micrograms.kg-1), which generate NO spontaneously, both increased calcium absorption with no change in mesenteric blood flow. When infused i.v., L-NAME (3 mg.hr-1.kg-1 for 40 min) induced a decrease in calcium absorption that was reversed by the NO donor sodium nitroprusside (1.5 mg.hr-1.kg-1 when infused for the last 20 min of the 40-min L-NAME infusion). Sodium nitroprusside infusion (1.5 mg.hr-1.kg-1) caused an increase in calcium absorption that was not reversed by L-NAME (3 and 30 mg.hr-1.kg-1). The present findings suggest that NO is involved in basal calcium absorption in rat small intestine in vivo.

Animals↗

Precocious and reversible expression of sucrase-isomaltase unrelated to intestinal cell turnover.

The effect of starvation and refeeding on the developmental pattern of intestinal sucrase-isomaltase (SI) was analyzed in preweaned rats. Starvation at postnatal day 12 caused a precocious expression of SI activity and mRNA. Alkaline phosphatase activity was slightly reduced, and no significant change was observed for aminopeptidase and lactase activities. Immunostaining showed that SI molecules appear in cells at the base of the villus. Sucrase expression was further increased by prolonged food deprivation, whereas enzyme activity as well as the amount of SI mRNA dropped to reach the low level found in control sucklings when 48 h-starved pups were refed by returning them to their dams. During the refeeding period, the enterocytes that were committed to produce SI by starvation continued to express the enzyme while migrating up the villi. However, the new epithelial cells arising from the crypts no longer synthesized the disaccharidase. The starvation-evoked appearance of SI was preceded by a transient burst of expression of the protooncogene c-fos, an event that may be correlated to the ontogenic rise of c-fos mRNA observed before weaning. However, in contrast to the normal weaning condition, SI induction by starvation occurred without obvious increase of epithelial cell proliferation and turnover. During the starvation and refeeding period, patterns of sucrase activity and SI mRNA paralleled the serum level of glucocorticoids.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

Polyamines and the recovery of intestinal morphology and function after ischemic damage in rats.

We have followed the time-course of the morphological and functional recovery of intestinal mucosa after 90 min of mesenteric vascular occlusion. At the end of the ischemic period the villi were smashed, but crypts were preserved. Microvillous hydrolase activities showed a dramatic drop when compared with sham-operated controls. Reperfusion was followed by an immediate upsurge of ornithine decarboxylase activity and a significant (p < 0.01) enhancement of putrescine and N1-acetyl-spermidine concentrations, while spermidine and spermine concentrations in mucosal cells decreased. This indicated that, both, de novo synthesis and degradation rates of the polyamines were increased. Treatment with alpha-difluoromethyl-ornithine, a selective inactivator of ornithine decarboxylase prevented the accumulation of active enzyme, but did not prevent morphological healing. It delayed however the recovery of sucrase and aminopeptidase-specific activities. Our results suggest that in addition to de novo synthesis, other sources of polyamines are mobilized to an extent that growth at a normal rate is supported. This indicates that the presence of active ornithine decarboxylase enzyme is not a prerequisite for the restitution of intestinal integrity after ischemia. We suggest that in a situation of inadequate polyamine supply the restoration of vital processes (mucosal regeneration) has priority over the restoration of specific functions.

Animals↗

Dietary calcium supplementation, blood pressure, and intestinal calcium absorption.

This study investigated the potential intestinal mechanism in the blood pressure-lowering effect of dietary calcium supplement. Adult Wistar rats received, through a gastrotomy cannula, either 5 or 30 mg elemental calcium.d-1 x 100 g BW-1 for 10 days. At day 11, mean arterial pressure was measured directly in anesthetized animals and calcium absorption determined using an in situ measurement technique of calcium absorption. An intestinal loop (duodenum and proximal jejunum) was perfused both by the intraluminal and the vascular routes. A solution containing 45Ca was perfused intraluminally and the 45Ca appearing in the venous effluent was determined to estimate calcium absorption. Oral calcium supplementation caused intestinal calcium uptake by the isolated loop to increase almost twofold. It also resulted in an 18% increase in mesenteric blood flow. The mean arterial pressure was decreased in calcium supplemented rats compared with control rats (87 +/- 5 vs. 78 +/- 5 mmHg; p < 0.05). These findings could indicate that the passive part of intestinal calcium transport increases in response to dietary calcium supplement. This improvement may participate in the blood pressure-lowering effect of a high calcium diet.

Animals↗

Development of a technique for in situ studies of calcium absorption in the intestine of rats.

The aim of the present study was to develop (feasibility, reliability, reproducibility) a technique for the in situ measurement of intestinal calcium absorption in the rat. An intestinal loop (duodenum+proximal jejunum) was perfused both by the intraluminal and vascular routes. A solution of NaCl 155 mM and CaCl2 1.25 mM containing 45Ca was perfused intraluminally at a flow rate of 0.2 ml/min and the 45Ca appearing in the venous effluent was determined to estimate calcium absorption. This technique was used to study the effect of a 10-day period of calcium supplementation on calcium absorption. The animals received enterally either 5 or 30 mg/day per kg BW. The results showed that intestinal calcium transport was enhanced when rats were given the calcium supplement for 10 days prior to the experiment (99.3 +/- 2.5 (n = 5) versus 36.6 +/- 3.6 (n = 5) nmol/min per kg BW, P < 0.001). This study indicates that dietary calcium supplement enhances calcium absorption probably by increasing the passive transport of calcium in the small intestine.

Animals↗

Comparison of different lipid substrates on intestinal adaptation in the rat.

The relative effects of medium chain (MCT) and long chain triglycerides (LCT) on intestinal morphology and functions were compared. Adult rats received intragastrically for 10 days an isoenergetic mixture containing either 50% MCT/50% LCT or 100% LCT. The other constituents of the diets were identical, and animals fed a standard diet orally were used as a reference group. Animals who were given the MCT/LCT diet showed a higher mucosal mass and protein content and increased villus length and crypt depth in the proximal part of the small intestine compared with the LCT and control diet groups. Administration of [3H] thymidine 12 hours before death resulted in a significant increase in the incorporation of the precursor into cellular DNA in the jejunum of rats given MCT. In rats given LCT as the only fat, the free fatty acid content of the microvillus membrane showed a 20 fold increase and at the same time there was a significant drop in the cholesterol content and in the cholesterol/protein ratio. Differences in the lipid composition of enterol diet or in the microvillus membrane did not effect adversely membrane bound hydrolase activities. These findings suggest that MCT in the diet confers advantages in addition to the provision of rapidly available energy.

Animals↗

Epidermal growth factor and the maturation of intestinal sucrase in suckling rats.

The regulatory effect of epidermal growth factor (EGF) on the postnatal maturation of sucrase was investigated in the small intestine of suckling and weanling rats. Administration of EGF (0.5 micrograms.g body wt-1.day-1) to suckling rats caused a slight precocious induction of sucrase expression. In weanling rats EGF markedly stimulated sucrase activity; however, at both ages, the effect of hydrocortisone was more potent. When the glucocorticoid antagonist RU-38486 was administered to sucklings, the precocious induction of sucrase activity by hydrocortisone was inhibited by 80%. However, RU-38486 or adrenalectomy did not prevent the inductive effect of EGF, indicating that EGF acts in a glucocorticoid-independent manner. EGF also potentiated the effect of hydrocortisone and dietary sucrose on the precocious induction of sucrase activity in the sucklings. At weaning, administration of an antiserum specific to rat EGF significantly decreased sucrase activity. This study shows the involvement of EGF in the postnatal maturation of intestinal sucrase in the rat.

Aging↗

Dietary control of the lactase mRNA distribution along the rat small intestine.

At weaning, the lactase-phlorizin hydrolase (LPH) mRNA was shown to disappear specifically from the distal part of ileum while remaining abundant in the more proximal segments of the small intestine. The purpose of this study was to analyze the longitudinal distribution of this transcript in rats whose intestinal lumen content was modified before and after weaning. Preweaned animals force-fed with an artificial diet retained a high amount of LPH mRNA in the jejunum, whereas this transcript precociously decreased in the distal ileum. Conversely, prolonged nursing delayed the specific decay of the LPH mRNA in the latter segment. Food deprivation in preweaned animals did not alter the longitudinal distribution of this transcript in that it remained abundant in the distal ileum. In adult rats, rearranging the order of the small intestinal segments with regard to the intraluminal flow of nutrients did not modify the typical distribution of the LPH mRNA. These results suggest that switching over from milk to the adult-type diet at weaning contributes to the modification of the longitudinal distribution of the LPH mRNA that normally occurs at this stage. However, once the adult pattern of expression of this transcript is established, it cannot be significantly altered by changing the position of each intestinal segment as well as its luminal content.

Aging↗

Adaptation of intestinal hydrolases to starvation in rats: effect of thyroid function.

The effects of long-term starvation on the activities of sucrase, lactase, and aminopeptidase, and on their respective mRNA were determined in the small intestine of thyroidectomized and sham-operated adult rats. Thyroidectomy reduced the protein loss at the level of the intestinal brush border membranes during starvation. Prolonged fasting caused a significant decrease in sucrase activity, but thyroidectomy partly prevented this effect. However, the amount of the corresponding mRNA dropped during long term starvation without incidence of thyroidectomy. Lactase activity in the brush border membranes was increased by starvation, and thyroidectomy caused a further elevation of the enzyme activity. Simultaneously, lactase mRNA content rose only slightly compared to the enzyme activity. Aminopeptidase activity and mRNA content decreased during starvation and thyroidectomy did not prevent this process. These results indicate that intestinal hydrolases respond non-coordinately to long-term food deprivation. In addition, the thyroid status of the animals has a direct influence on the adaptation of several brush border hydrolases to starvation. This suggests that the drop in plasma thyroid hormones during fasting allows a better maintenance of protein content and of hydrolase activities in the brush border membranes of the small intestine. These adaptive processes seemed to be partly controlled at a post-transcriptional level.

Adaptation, Physiological↗

Lactase expression is controlled differently in the jejunum and ileum during development in rats.

This study shows the distribution of the messenger RNA for lactase-phlorizin hydrolase during postnatal development and along the longitudinal axis of the rat small intestine. At birth, this messenger RNA was present along the whole length of small intestine, and its concentration remained elevated during the suckling period despite the concomitant decrease in enzyme activity. At weaning, the amount of lactase messenger RNA dropped specifically in the distal ileum. This decrease in lactase messenger RNA was initiated at the ileocecal junction, progressed gradually towards the jejunum, and followed the decrease in lactase activity several days later. Starvation and refeeding were also found to cause modifications of lactase activity and messenger RNA expression that were prominent in the distal part of small intestine. These data support that posttranscriptional and pretranslational levels of regulation are required to define the spatial and temporal expression of lactase in the rat small intestine.

Animals↗

Ileal compensation for age-dependent loss of jejunal function in rats.

Adaptive responses of brush border hydrolases and crypt cell proliferation were measured in the jejunum and ileum of 4-mo-old adult and 28-mo-old senescent male Wistar rats. Responses were measured after rats were deprived of food and then refed with a normoprotein diet (17% protein) or an isoenergetic high protein diet (70% protein). The young rats deprived of food then refed for 18 h with the high protein diet showed better body weight recovery than did old animals. Withholding food for 48 h induced a more pronounced drop of sucrase activity in the intestine of the old rats relative to young rats. Refeeding the high protein diet caused a better recovery of sucrase activity in the jejunum of young rats relative to senescent rats. In the aged animals, sucrase activity in the jejunum remained significantly lower after refeeding both diets. Compared with nourished controls, aged rats showed enzyme activity to be completely restored in the ileum. The high protein diet increased aminopeptidase activity in the jejunum and ileum of young rats, in contrast to the senescent rats in which the increase of enzyme activity was restricted to the ileum. In the jejunum of aged rats, the cell migration rate from crypt base to villus tip was reduced after refeeding, but no age-related changes were observed in the ileum. Our results indicate that the jejunum of senescent rats exhibits reduced adaptive capacities that may be partly compensated by enhanced ileal functions.

Adaptation, Physiological↗

Derivatives of plant beta-glucans are hydrolyzed by intestinal lactase-phlorizin hydrolase of mammals.

Laminaribiose and gentiobiose, two O-beta-linked disaccharides deriving from plant beta-glucans, were found to be hydrolyzed in the rat small intestine by an enzyme anchored into the brush border membrane of the enterocytes. Immunological and biochemical data, together with the developmental pattern of expression, support that this activity is carried out by the bifunctional enzyme involved in the hydrolysis of lactose and glycosylceramides: the lactase-phlorizin hydrolase complex.

Animals↗

Rat lactase activity and mRNA expression in relation to the thyroid and corticoid status.

The effect of glucocorticoids and thyroid hormones on lactase expression was investigated along the small intestine of rats. In sucklings thyroxine injections promoted a precocious drop of enzyme activity but not of mRNA. Hydrocortisone did neither modify lactase activity nor its mRNA expression. In adults decreasing the amount of thyroid hormones led to a slight and reversible increase of the lactase mRNA content whereas lactase activity rised more dramatically. Thus, thyroid hormones in contrast to corticoids, are involved in the posttranscriptional control of lactase during the suckling period. Yet, none of these hormones might induced the modification of the longitudinal distribution of the lactase mRNA that occurred at weaning.

Animals↗

Specific expression of lactase in the jejunum and colon during postnatal development and hormone treatments in the rat.

The expression of lactase was compared in the jejunum and colon of the rat at the levels of enzyme activity and protein and RNA content. We found that the enzyme proteins and the corresponding mRNAs share common features and are encoded by a single gene in both intestinal segments. In the jejunum, large amounts of lactase mRNA and proteins were detected during postnatal development as well as in adult rats, despite the 10-fold decline in lactase specific activity which occurs at weaning. In contrast, in the colon the expression of lactase was restricted to early postnatal development. In the colon, the enzymic activity of lactase and the amounts of protein and mRNA followed parallel development profiles with a peak at day 4 after birth. Injections of thryoxine or epidermal growth factor into neonates led to small modifications in the expression of lactase in the jejunum. On the other hand, these treatments caused a large decline in lactase activity in the colon that paralleled a decrease in the amount of lactase protein and mRNA. These data indicate that the expression of lactase is mainly regulated at the post-transcriptional level in the jejunum, whereas it is controlled at the pretranslational level in the colon.

Animals↗

Effect of epidermal growth factor on the expression of digestive hydrolases in the jejunum and colon of newborn rats.

The regulatory effect of epidermal growth factor (EGF) on the developmental pattern of brush border hydrolases was studied in the proximal jejunum and colon of the newborn rat. In the proximal colon, daily administration of EGF for 1, 3, or 5 days postpartum inhibited the postnatal increase in lactase, maltase, and aminopeptidase specific activities. In contrast, in the jejunum EGF did not influence lactase activity, inconsistently increased maltase activity, and partly prevented the early postnatal decrease in aminopeptidase activity. In the proximal colon, EGF showed additive effects with T4 and hydrocortisone on the inhibition of lactase activity. In the jejunum, EGF potentiated the effect of hydrocortisone and T4 on the expression of sucrase activity and had only a slight effect when injected alone. The incorporation rate of [3H]thymidine in the proximal colon and jejunum was not different in control and treated rats, indicating the absence of an effect of EGF on DNA synthesis. These results show that EGF may play an important physiological role in the enzymatic differentiation of the developing intestine during early postnatal development. Alone or acting with T4 or glucocorticoids, EGF may induce the decline of digestive hydrolases in the proximal colon. In the small intestine EGF may play a major role in the triggering of sucrase expression.

Aminopeptidases↗