Dietary induction of angiotensin-converting enzyme in proximal and distal rat small intestine

2001 ◽  
Vol 281 (5) ◽  
pp. G1221-G1227 ◽  
Author(s):  
Roger H. Erickson ◽  
Byung-Chul Yoon ◽  
Danielle Y. Koh ◽  
Do Hyong Kim ◽  
Young S. Kim

Induction of angiotensin-converting enzyme was examined in proximal and distal intestinal segments of rats fed a low-protein (4%) diet and then switched to a high-protein (gelatin) diet. Animals were killed at varying time points, and brush-border membranes and total RNA were prepared from the segments. In the proximal intestine, there was a fivefold increase in angiotensin-converting enzyme levels after 14 days but only a twofold change in mRNA. In the distal intestine, there was no increase in enzyme activity but mRNA increased 2.4-fold. Organ culture was used to measure changes in enzyme biosynthesis. There was a 5- to 6-fold increase in the biosynthesis of angiotensin-converting enzyme in the proximal intestine 24 h after the switch to the gelatin diet and a 1.6-fold increase in mRNA levels. No change in biosynthesis was observed in the distal small intestine despite an increase in mRNA. These results support the conclusion that rapid dietary induction of intestinal angiotensin-converting enzyme is differentially regulated in proximal and distal segments of the small intestine.

1993 ◽  
Vol 72 (2) ◽  
pp. 312-318 ◽  
Author(s):  
H Schunkert ◽  
J R Ingelfinger ◽  
A T Hirsch ◽  
Y Pinto ◽  
W J Remme ◽  
...  

Endocrinology ◽  
2007 ◽  
Vol 148 (5) ◽  
pp. 2453-2457 ◽  
Author(s):  
Shigeyuki Wakahara ◽  
Tadashi Konoshita ◽  
Shinichi Mizuno ◽  
Makoto Motomura ◽  
Chikako Aoyama ◽  
...  

Angiotensin-converting enzyme (ACE) 2, a newly emerging component of the renin-angiotensin system, is presumed to be a counterregulator against ACE in generating and degrading angiotensin II. It remains to be elucidated how mRNA levels of these two genes are quantitatively regulated in the kidney and also what kind of clinicopathological characteristics could influence the gene expressions in humans. Seventy-eight cases of biopsy-proven renal conditions were examined in detail. Total RNA from a small part of each renal cortical biopsy specimen was reverse transcribed, and the resultant cDNA was amplified for ACE, ACE2, and glyceraldehyde-3-phosphate dehydrogenase with a real-time PCR system. Then we investigated the relationship between clinicopathological variables and mRNA levels adjusted for glyceraldehyde-3-phosphate dehydrogenase. Statistically significant correlation was not observed between any clinicopathological variables and either of the gene expressions by pairwise comparison. However, a strong correlation was observed between the gene expressions of ACE and those of ACE2. Moreover, the ACE to ACE2 ratio was significantly higher in subjects with hypertension (HT) than that in subjects without HT. Whereas parameters of renal function, e.g. urinary protein excretion (UPE) and creatinine clearance (Ccr), are not significantly related to the ACE to ACE2 ratio as a whole, the HT status may reflect disease-induced deterioration of renal function. That is, UPE and Ccr of subjects with HT are significantly different from those without HT, in which a significant correlation is also observed between UPE and Ccr. Finally, stepwise regression analysis further revealed that only the HT status is an independent confounding determinant of the ACE to ACE2 ratio among the variables tested. Our data suggest that ACE2 might play an important role in maintaining a balanced status of local renin-angiotensin system synergistically with ACE by counterregulatory effects confounded by the presence of hypertension. Thus, ACE2 may exert pivotal effects on cardiovascular and renal conditions.


2021 ◽  
Vol 9 ◽  
Author(s):  
Roberto Berni Canani ◽  
Marika Comegna ◽  
Lorella Paparo ◽  
Gustavo Cernera ◽  
Cristina Bruno ◽  
...  

Background: Clinical features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection seem to differ in children compared to that in adults. It has been hypothesized that the lower clinical severity in children could be influenced by differential expression of the main host functional receptor to SARS-CoV-2, the angiotensin-converting enzyme 2 (ACE2), but data are still conflicting. To explore the origin of age-dependent clinical features of coronavirus disease 2019 (COVID-19), we comparatively evaluated the expression in children and adult subjects of the most relevant mediators of the SARS-CoV-2 infection: ACE2, angiotensin-converting enzyme 1 (ACE1), transmembrane serine protease-2 (TMPRSS2), and neuropilin-1 (NRP1), at upper respiratory tract and small intestine level.Methods: The expression of ACE2, ACE1, TMPRSS2, and NRP1 in nasal epithelium and in small intestine epithelium was investigated by quantitative real-time PCR analysis.Results: We found no differences in ACE2, ACE1, and TMPRSS2 expression in the nasal epithelium comparing children and adult subjects. In contrast, nasal epithelium NRP1 expression was lower in children compared to that in adults. Intestinal ACE2 expression was higher in children compared to that in adults, whereas intestinal ACE1 expression was higher in adults. Intestinal TMPRSS2 and NRP1 expression was similar comparing children and adult subjects.Conclusions: The lower severity of SARS-CoV-2 infection observed in children may be due to a different expression of nasal NRP1, that promotes the virus interaction with ACE2. However, the common findings of intestinal symptoms in children could be due to a higher expression of ACE2 at this level. The insights from these data will be useful in determining the treatment policies and preventive measures for COVID-19.


Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Douglas M Bennion ◽  
Emily Haltigan ◽  
Alexander J Irwin ◽  
Daniel L Purich ◽  
Colin Sumners

Background: Recent studies show that pharmacological induction of the angiotensin converting enzyme 2/angiotensin-(1-7)/mas [ACE2-Ang-(1-7)-Mas] axis, a protective pathway of the renin angiotensin system, elicits neuroprotection in ischemic stroke. However, endogenous levels and activity of the components of this axis in the brain and serum following stroke are not well established. Here, we assessed the post-stroke activity and expression of ACE2 in rat cerebral cortex and serum after ischemic stroke in rats, in the absence or presence of an ACE2 activator. Methods: Sprague Dawley rats underwent sham surgery or endothelin-1-induced middle cerebral artery occlusion (ET-1 MCAO). Activity of ACE2 was analyzed within serum and cerebral cortical tissue samples using a fluorometric assay, and mRNA levels were assessed by qRT-PCR. In an additional experiment, rats received daily intraperitoneal administration of diminazene aceturate (DIZE), a putative ACE2 activator, or vehicle after ET-1 MCAO. Data are normalized to corresponding control values and expressed as means ± SEM with a significance of p<0.05. Results: ACE2 activity levels were significantly increased in ischemic brain cortex at 4, 12, and 24 h after a stroke (4h: 237.1±46.1%; 12h: 212.4±12.8%; 24h: 191.6±19.1%) versus rats with sham strokes. Paradoxically, there was a significant decrease in ACE2 mRNA levels in the ischemic cortex at 24h (0.71±0.1) compared to shams (1.0±0.08). After decreasing in activity at 4h after stroke, serum ACE2 activity was increased at 24h in stroked rats (96.08±9.4%) versus shams (70.80±7.1%). Post-stroke treatment with DIZE (7.5 mg/kg) resulted in significantly increased ACE2 activity in serum (213.7±49.8%) versus controls, two days following stroke. Conclusions: Activity of the protective enzyme ACE2 is increased in rat cerebral cortex following stroke, with a rebound increase in serum activity. Post-stroke treatment with an ACE2 activator resulted in significantly increased ACE2 activity in serum. These results suggest that stroke therapeutics designed to target the ACE2/Ang-(1-7)/Mas axis may act in synergy with endogenous changes in the acute post-stroke setting, lending promise to their further study as potential neuroprotective agents.


1981 ◽  
Vol 240 (2) ◽  
pp. G141-G146
Author(s):  
H. S. Ormsbee ◽  
G. L. Telford ◽  
C. M. Suter ◽  
P. D. Wilson ◽  
G. R. Mason

This study quantitatively evaluated the characteristics of the aboral propagation of the canine migrating motor complex (MMC). Five conscious dogs were implanted with extraluminal force transducers along the small intestine. After constructing a 30-cm Thirty-Vella loop of jejunum, 56 of 91 activity fronts were outside the tolerance limits for propagation from the proximal intestine to the loop established in the same dogs before operation. Similarly, 44 of 109 activity fronts were outside the tolerance limits for propagation from the loop to the distal intestine. After surgery, the propagation time from the proximal jejunum to the loop was significantly increased, and activity fronts were observed to originate in the loop and in the intestine distal to the anastomosis. Our study indicates that the hypothesis that extrinsic nerves alone control the migration of the MMC is incomplete. We suggest that the extrinsic and the intrinsic innervation of the gastrointestinal tract are both required for the precise pattern of the migration of the MMC.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Nisha Sharma ◽  
Anil Bhanudas Gaikwad

Abstract Background and Aims In clinical settings, diabetics remain on higher risk of ischemic renal injury (IRI) than nondiabetic patients. In addition, IRI predisposes distant organs to dysfunction such as neurological impairments via activation of the pressor arm of renin-angiotensin system (RAS). In contrast, the role of depressor arm of RAS on IRI-associated neurological sequalae remains elusive. Hence, this study explored the role of angiotensin II type 2 receptor (AT2R) and angiotensin-converting enzyme 2 (ACE2) in IRI-associated neurological dysfunctions under nondiabetic (ND) and diabetes mellitus (DM) condition. Method Type 1 diabetes was induced by injecting streptozotocin (55 mg/kg i.p.). ND and DM rats with bilateral IRI were treated with AT2R agonist-Compound 21 (C21) (0.3 mg/kg/day, i.p.) or ACE2 activator-Diminazene Aceturate (Dize), (5 mg/kg/day, p.o.) per se or in combination therapy. Behavioural, biochemical, and histopathological analysis were done to assess IRI-induced neurological impairment. Moreover, immunohistochemistry, ELISA and qRT-PCR experiments were conducted for molecular mechanism analysis. Result In ND and DM rats, IRI caused hippocampal complications as evidenced by increased MDA and nitrite levels, augmented inflammatory cytokines (granulocyte colony stimulating factor, glial fibrillary acidic protein), altered protein and mRNA expressions of Ang II, Ang-(1-7), AT1R, AT2R and MasR. In contrast, concomitant therapy of C21 and Dize effectively normalised aforementioned hippocampal alterations. The protective effect of combination therapy was exerted due to augmented protein and mRNA levels of depressor arm components. Conclusion The current study demonstrated the protective role of AT2R agonist and ACE2 activator in IRI-associated neurological dysfunction through preventing oxidative stress, inflammation and upregulating brain depressor arm of RAS under ND and DM conditions.


Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2348
Author(s):  
Shilpa Tejpal ◽  
Alan M. Wemyss ◽  
Claire C. Bastie ◽  
Judith Klein-Seetharaman

Obesity is associated with insulin resistance and cardiovascular complications. In this paper, we examine the possible beneficial role of lemon juice in dieting. Lemon extract (LE) has been proposed to improve serum insulin levels and decrease angiotensin converting enzyme (ACE) activity in mouse models. ACE is also a biomarker for sustained weight loss and ACE inhibitors improve insulin sensitivity in humans. Here, we show that LE impacts adipose tissue metabolism directly. In 3T3-L1 differentiated adipocyte cells, LE improved insulin sensitivity as evidenced by a 3.74 ± 0.54-fold increase in both pAKT and GLUT4 levels. LE also induced lipolysis as demonstrated by a 16.6 ± 1.2 fold-change in pHSL protein expression levels. ACE gene expression increased 12.0 ± 0.1 fold during differentiation of 3T3-L1 cells in the absence of LE, and treatment with LE decreased ACE gene expression by 80.1 ± 0.5% and protein expression by 55 ± 0.37%. We conclude that LE’s reduction of ACE expression causes increased insulin sensitivity and breakdown of lipids in adipocytes.


1989 ◽  
Vol 26 (5) ◽  
pp. 376-385 ◽  
Author(s):  
A. C. Huber ◽  
R. H. Yolken ◽  
L. C. Mader ◽  
J. D. Strandberg ◽  
S. L. Vonderfecht

Suckling rats were inoculated with a group B rotavirus to determine the progression of the morphologic changes induced in the intestine by this virus. Several changes were observed by light microscopy 1 day after viral inoculation: shortening of small intestinal villi, villous epithelial necrosis, and villous epithelial syncytia. The lesions were most often present in the distal small intestine, although other small intestinal segments were affected to a lesser degree. By day 3 post-inoculation, epithelial necrosis, and syncytia were no longer present; however, the villous epithelium was disorganized and irregularly vacuolated, and intestinal crypt epithelium was hyperplastic. Alterations in villous height to crypt depth ratios were present in portions of the small intestine for the remainder of the 12-day study period. Epithelial syncytia appeared to form by the breakdown of the lateral interdigitating membranes of the absorptive villous epithelium. Viral particles, abundant in the syncytia, appeared to form from amorphous or reticular arrays of viral precursor material. Group B rotaviral antigens, as detected by indirect immunofluorescence, were present in large amounts in the small intestinal villous epithelium only on the first day after viral inoculation. These studies show that two important diagnostic features of group B rotaviral infections of rats, epithelial syncytia and viral antigen as determined by immunofluorescence, are present only on the first day of disease. These findings should be taken into consideration when attempting to diagnose disease induced by this agent.


1992 ◽  
Vol 11 (3) ◽  
pp. 189-200 ◽  
Author(s):  
J. Meulenbelt ◽  
L. van Bree ◽  
J.A.M.A. Dormans ◽  
A.B.T.J. Boink ◽  
B. Sangster

1 In previous studies a rat inhalation model was developed to investigate the treatment of acute nitrogen dioxide (NO2) intoxication. 2 Biochemical parameters, which may be important for the evaluation of lung injury and repair, were reviewed and compared with the histology. 3 After exposure to high NO2 concentrations (75 ppm, 125 ppm or 175 for 10 min) 1 the lung injury observed by light microscope was most pronounced after 24 h and became worse with increasing concentration. 4 The most sensitive indicators for lung injury in the broncho-alveolar lavage fluid (BAL) were protein and albumin concentrations, angiotensin converting enzyme activity, β-glucuronidase activity and the presence of neutrophil leucocytes. The changes observed in these variables were dose-dependent. Following exposure to 175 ppm the protein and albumin concentrations and the angiotensin converting enzyme activity showed a 100-fold increase, while the β-glucuronidase activity showed a 10-fold increase. 5 Glucose-6-phosphate dehydrogenase and glutathione peroxidase in the supernatant of lung homogenate and gamma-glutamyl transferase activity in BAL are likely to be the most practical parameters for monitoring the phase of repair because their activities were maximal at the moment histological changes were reduced in intensity. 6 Repair was almost complete 7 d following exposure.


Sign in / Sign up

Export Citation Format

Share Document