A growth-stimulating activity derived from the proximal small intestine is associated with an adaptive response

1990 ◽  
Vol 68 (5) ◽  
pp. 646-649 ◽  
Author(s):  
V. L. Grey ◽  
C. L. Morin
Keyword(s):  
Cell Proliferation ◽  
Small Intestine ◽  
Thymidine Kinase ◽  
Kinase Activity ◽  
Crypt Cell ◽  
General Mechanism ◽  
Cell Renewal ◽  
Thymidine Kinase Activity ◽  
Crypt Cell Proliferation ◽  
Proximal Intestine

Luminal nutrition is important for the maintenance of small intestinal structure and function. The equilibrium between crypt cell production and villous cell loss in the mucosal epithelium of the small intestine is altered under certain conditions such as after a small bowel resection. Immediately after resection, there is a marked increase in crypt cell proliferation giving rise to an adaptive hyperplasia in the remnant intestine and for this response luminal nutrition is a critical factor. We have previously demonstrated the presence of a growth-stimulating (GS) activity in a heat-stable acidic extract of the rat proximal intestine 24, 48, and 96 h after resection, which is coincidental with an increase in crypt cell proliferation as measured by thymidine kinase activity. Eight days after resection when the GS activity is no longer detectable, the thymidine kinase activity returns to control values. The molecular weights of the peptides associated with this GS activity are 4500 and 1500, as determined by Sephadex gel filtration. Of note is that the oral intake of food is necessary for the appearance of the GS activity postoperatively. The presence of the GS activity has also been demonstrated upon refeeding after a fast, as well as at weaning in the rat, two physiological situations known to be associated with increased proliferation in the small intestine. This GS activity in the proximal intestine first detected in the resection model may represent a general mechanism by which food controls the cell renewal pattern of the small intestine.Key words: stimulating activity, proximal intestine, adaptation.

ANF-C-receptor-mediated inhibition of aortic smooth muscle cell proliferation and thymidine kinase activity

1994 ◽  
Vol 266 (1) ◽  
pp. R194-R203 ◽  
Author(s):  
P. A. Cahill ◽  
A. Hassid
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Dna Synthesis ◽  
Thymidine Kinase ◽  
Receptor Binding ◽  
Kinase Activity ◽  
Thymidine Kinase Activity ◽  
Aortic Smooth Muscle ◽  
Inhibition Of Dna Synthesis ◽  
Type Receptor

We have investigated the inhibition of DNA synthesis and cell proliferation by rat atrial natriuretic factor [rANF-(99-126)] and several synthetic peptides that bind selectively to the ANF-C-type clearance receptors in subcultured aortic smooth muscle cells. These peptides decreased serum-induced 1) [3H]thymidine incorporation, 2) cell proliferation, and 3) thymidine kinase activity without altering basal or elevated cAMP or cGMP levels. In contrast, another ANF-C-receptor-binding peptide, des[Gln116,Ser117,Gly118,Leu119,Gly120] rANF-(102-121)-NH2 (cANF), failed to decrease serum-induced mitogenesis, yet 100 nM cANF reversed the inhibition of DNA synthesis and cell proliferation and the decrease of thymidine kinase activity elicited by other C receptor-binding peptides, including rANF-(99-126), rANF-(103-125), and porcine C-type natriuretic peptide [pCNP-(1-22)]. Delayed addition experiments indicated that atrial peptides influence a relatively late event (or events) during the G1 phase of the cell cycle. The inhibition of DNA synthesis by C-receptor-binding atrial peptides appeared to be selective for aortic smooth muscle cells, inasmuch as a potent inhibitory agonist peptide, Cys116-rANF-(102-116), was without significant influence on the incorporation of thymidine in cultured rat mesangial cells or bovine pulmonary artery endothelial cells. These results indicate that atrial natriuretic peptide analogues decrease vascular smooth muscle cell mitogenesis and proliferation by a cyclic nucleotide-independent mechanism involving the C-type receptor. Moreover the inhibition of DNA synthesis by rANF-(99-126) and the neuropeptide pCNP-(1-22) appears to be mediated by the ANF-C-type receptor and is associated with inhibition of thymidine kinase activity.

Nutrient-stimulated GLP-2 release and crypt cell proliferation in experimental short bowel syndrome

2005 ◽  
Vol 288 (3) ◽  
pp. G431-G438 ◽  
Author(s):  
G. R. Martin ◽  
L. E. Wallace ◽  
B. Hartmann ◽  
J. J. Holst ◽  
L. Demchyshyn ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Time Course ◽  
Intestinal Adaptation ◽  
Intestinal Resection ◽  
Small Bowel Resection ◽  
Crypt Cell ◽  
Crypt Cell Proliferation ◽  
Proximal Intestine ◽  
The Relationship ◽  
Over Time

Glucagon-like peptide-2 (GLP-2) is an enteroendocrine peptide that is released in response to luminal nutrients and has unique trophic actions in the gastrointestinal tract. These features suggest GLP-2 may be important in controlling intestinal adaptation. We examined the relationship over time of GLP-2 production and adaptation to intestinal resection, the effects of resection-induced malabsorption on GLP-2 production, and the correlation of endogenous serum GLP-2 levels with adaptation as measured by crypt-cell proliferation (CCP). We initially examined the effect of nutrient malabsorption, induced by a 90% resection of the proximal intestine studied on day 4, on the time course and levels of GLP-2 release. Secondly, the degree of malabsorption was varied by performing intestinal transection or 50, 75, or 90% resection of proximal small intestine. Finally, the relationship of GLP-2 levels over time with adaptation to a 90% resection was examined by determining GLP-2 levels on days 7, 14, and 28, and correlating this with intestinal adaptation, as assessed by morphology and CCP rate. A 90% resection significantly increased basal and postprandial GLP-2 levels, with a net increase in nutrient-stimulated exposure over 90 min; GLP-2 exposure (integrated levels vs. time) increased 12.7-fold in resected animals ( P < 0.001). Basal and postprandial GLP-2 levels significantly correlated with the magnitude of intestinal resection ( r2 = 0.71; P < 0.001), CCP ( r2 = 0.48; P < 0.005), and nutrient malabsorption (protein, P < 0.001; fat, P < 0.005). The increase in CCP was maintained to 28 days after small bowel resection and was associated with an ongoing elevation in GLP-2 release. These findings suggest that GLP-2 is important in initiating and maintaining the small intestinal adaptive response to resection.

scholarly journals The Effect of Ischemic Villus Cell Damage on Crypt Cell Proliferation in the Small Intestine

1976 ◽  
Vol 71 (5) ◽  
pp. 786-792 ◽  
Author(s):  
R.P.C. Rijke ◽  
W.R. Hanson ◽  
H.M. Plaisier ◽  
J.W. Osborne
Keyword(s):  
Cell Proliferation ◽  
Small Intestine ◽  
Cell Damage ◽  
Crypt Cell ◽  
Crypt Cell Proliferation ◽  
Villus Cell

scholarly journals Spdef deletion rescues the crypt cell proliferation defect in conditional Gata6 null mouse small intestine

2014 ◽  
Vol 15 (1) ◽  
pp. 3 ◽  
Author(s):  
Boaz E Aronson ◽  
Kelly A Stapleton ◽  
Laurens ATM Vissers ◽  
Eva Stokhuijzen ◽  
Hanneke Bruijnzeel ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Small Intestine ◽  
Crypt Cell ◽  
Null Mouse ◽  
Crypt Cell Proliferation ◽  
Mouse Small Intestine

Thymidine kinase, thymidylate synthase, and endothelial cell growth under hyperoxia

1987 ◽  
Vol 62 (1) ◽  
pp. 10-14 ◽  
Author(s):  
A. F. Junod ◽  
H. Petersen ◽  
L. Jornot
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Dna Synthesis ◽  
Thymidine Kinase ◽  
Thymidylate Synthase ◽  
Kinase Activity ◽  
Primary Cultures ◽  
Thymidine Kinase Activity ◽  
Aortic Endothelial Cells ◽  
Key Enzyme

To determine the respective role of thymidine kinase and thymidylate synthase activities in the hyperoxia-induced decrease in DNA synthesis and their relationship with cell replication, we measured these two enzyme activities in primary cultures of porcine aortic endothelial cells under different O2 concentrations for various durations. In confluent cells, exposure to 95% O2 for 5 days reduced thymidine kinase activity to 15% of control values; thymidylate synthase activity was unaffected. In preconfluent cells exposed to 95% O2 for 2 days, similar results were obtained, together with evidence for arrest in cell proliferation. Thymidylate synthase activity could therefore not be related to decreased cell proliferation under hyperoxia. [3H]thymidine incorporation into DNA, thymidine kinase activity, and cell proliferation were all similarly affected under exposure to graded O2 concentration for 2 days. Thymidine kinase appears to be a key enzyme in the modulation of DNA synthesis from thymidine and in its replication in endothelial cells.

Gastric mucosal cell proliferation during development in rats and effects of pentagastrin

1982 ◽  
Vol 242 (2) ◽  
pp. G135-G139 ◽  
Author(s):  
A. P. Majumdar ◽  
L. R. Johnson
Keyword(s):  
Cell Proliferation ◽  
Dna Synthesis ◽  
Thymidine Kinase ◽  
Kinase Activity ◽  
Cell Loss ◽  
Saline Control ◽  
Mucosal Cell ◽  
Thymidine Kinase Activity ◽  
Old Rats

Changes in cell proliferation and cell loss in the gastric mucosa were examined during the first 4 wk of life. The effect of pentagastrin on these parameters before and after weaning was also investigated. The results revealed that DNA content of mucosa and lumen increased with age. However, when luminal DNA (an assessment of cell loss) content was expressed as percent of total mucosal DNA (referred to as percent cell loss), an inverse relationship with age was observed. The rate of mucosal DNA synthesis, measured in vitro, was found to remain elevated up to the age of 15 days and then dropped dramatically within the next 5--6 days after which it decreased slowly. The rate of mucosal DNA synthesis in 5- to 15-day-old rats was found to be 10--15 times higher than in 20- to 30-day-old rats. In 10-day-old suckling young, mucosal thymidine kinase activity was also found to be higher than in 20- to 28-day-old rats. On the other hand, total incorporation of [3H]thymidine into mucosal DNA per stomach was found to be significantly greater in 21- to 28-day-old weaned rats than in the 10-day-old suckling young. Multiple injections of pentagastrin to 28-day-old rats significantly increased mucosal DNA synthesis and thymidine kinase activity by 43 and 200%, respectively, and cell loss by 30% when compared with the saline control. The hormone did not affect DNA synthesis, thymidine kinase, or cell loss in 10-day-old rats. There were considerable increases in 20-day-old rats that were not statistically significant due to the variation of the data.

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