| 1. |
- Nilsson, Åke, et al.
(författare)
-
Pancreatic and mucosal enzymes in choline phospholipid digestion
- 2019
-
Ingår i: American Journal of Physiology: Gastrointestinal and Liver Physiology. - : American Physiological Society. - 1522-1547 .- 0193-1857. ; 316:4, s. 425-445
-
Tidskriftsartikel (refereegranskat)abstract
- The digestion of choline phospholipids is important for choline homeostasis, lipid signaling, postprandial lipid and energy metabolism, and interaction with intestinal bacteria. The digestion is mediated by the combined action of pancreatic and mucosal enzymes. In the proximal small intestine, hydrolysis of phosphatidylcholine (PC) to 1-lyso-PC and free fatty acid (FFA) by the pancreatic phospholipase A2 IB coincides with the digestion of the dietary triacylglycerols by lipases, but part of the PC digestion is extended and must be mediated by other enzymes as the jejunoileal brush-border phospholipase B/lipase and mucosal secreted phospholipase A2 X. Absorbed 1-lyso-PC is partitioned in the mucosal cells between degradation and reacylation into chyle PC. Reutilization of choline for hepatic bile PC synthesis, and the reacylation of 1-lyso-PC into chylomicron PC by the lyso-PC-acyl-CoA-acyltransferase 3 are important features of choline recycling and postprandial lipid metabolism. The role of mucosal enzymes is emphasized by sphingomyelin (SM) being sequentially hydrolyzed by brush-border alkaline sphingomyelinase (alk-SMase) and neutral ceramidase to sphingosine and FFA, which are well absorbed. Ceramide and sphingosine-1-phosphate are generated and are both metabolic intermediates and important lipid messengers. Alk-SMase has anti-inflammatory effects that counteract gut inflammation and tumorigenesis. These may be mediated by multiple mechanisms including generation of sphingolipid metabolites and suppression of autotaxin induction and lyso-phosphatidic acid formation. Here we summarize current knowledge on the roles of pancreatic and mucosal enzymes in PC and SM digestion, and its implications in intestinal and liver diseases, bacterial choline metabolism in the gut, and cholesterol absorption.
|
|
| 2. |
- Andersson, Lena, et al.
(författare)
-
Pancreatic lipase related protein 2, but not classical lipase hydrolyzes galactolipids
- 1996
-
Ingår i: Biochimica et Biophysica Acta. - : Elsevier BV. - 0006-3002. ; 1302:3, s. 236-240
-
Tidskriftsartikel (refereegranskat)abstract
- The pancreatic lipase family contains three subfamilies, the 'classical' lipases and the pancreatic lipase-related proteins 1 (PLRP1) and 2 (PLRP2). Galactolipids are present in membranes of leaves and vegetables and consist of digalactosyldiacylglycerol (DGalDG) monogalactosyldiacylglycerol (MGalDG) and sulfoquinovosyldiacylglycerol (SQDG). These lipids were incubated with PLRP2 from guinea-pig (GPLRP2) and rat (RPLRP2). In the presence of bile salts DGalDG was efficiently hydrolyzed by GPLRP2 and, although less efficiently, by RPLRP2 to digalactosylmonoacylglycerol (DGalMG), free fatty acids and water-soluble galactose-containing compounds. Also, MGalDG and SQDG were hydrolyzed by GPLRP2 and RPLRP2. These data suggest a possible role of PLRP2 in the digestion of dietary galactolipids
|
|
| 3. |
|
|
| 4. |
- Barros, H., et al.
(författare)
-
Hydrolysis of phosphatidylinositol by human panreatic phospholipase A2
- 1990
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 25:2, s. 134-140
-
Tidskriftsartikel (refereegranskat)abstract
- Pure human pancreatic phospholipase A2 efficiently hydrolyzed the 2-ester bond of 14C-2-linoleoyl and 14C-2-arachidonyl phosphatidylinositol (PI). The rate of hydrolysis varied markedly with the bile salt (sodium taurocholate to sodium taurodeoxycholate, 3:4 mol/mol) concentration, the hydrolysis being decreased with increasing bile salt to PI ratio. The influence of bile salts was thus similar to that which has earlier been described for the hydrolysis of phosphatidylcholine (PC) with pig pancreatic phospholipase A2. When 2-3H-arachidonyl PC and 2-14C-arachidonyl PI were incorporated into a mixed substrate, PI was hydrolyzed even faster than PC, the hydrolysis of both phospholipids varying in the same manner with bile salt concentration. 2-14C-arachidonyl PI was also efficiently hydrolyzed by human duodenal content, although at a somewhat slower rate than 2-3H-arachidonyl PC. It is concluded that PI is a good substrate for human phospholipase A2. This minor but arachidonate-rich dietary phospholipid may thus be digested and absorbed by pathways similar to those of the major dietary and bile phospholipid, phosphatidylcholine.
|
|
| 5. |
- Benoni, Cecilia, et al.
(författare)
-
Smoking habits in patients with inflammatory bowel disease. A case control study.
- 1987
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 22:9, s. 1130-1136
-
Tidskriftsartikel (refereegranskat)abstract
- In a case-control study there were significantly fewer smokers among patients with ulcerative colitis both at disease onset and at interview, the relative risk compared with non-smokers being 0.33 and 0.12, respectively. Among female patients with Crohn's disease there were significantly more smokers, the relative risk being 2.70 and 2.33, respectively. Of the ex-smokers with ulcerative colitis, two-thirds became ill after they stopped smoking, and most of these during the first years after stopping. Neither in ulcerative colitis nor in Crohn's disease could any relation be found between the localization of disease and smoking habits at the time of diagnosis. The findings in the present study support the hypothesis that smoking may influence the course of inflammatory bowel disease
|
|
| 6. |
- Chen, Qi, et al.
(författare)
-
Digestion of triacylgycerols containing longchain polyenoic fatty acids in vitro by colipase dependent lipase and human milk bile salt stimulated lipase
- 1994
-
Ingår i: Biochimica et Biophysica Acta. - : Elsevier BV. - 0006-3002. ; 121:2, s. 239-243
-
Tidskriftsartikel (refereegranskat)abstract
- To assess the role of human milk bile salt-stimulated lipase (BSSL) in the digestion of polyunsaturated ester bonds of triacylglycerols, hydrolysis of docosahexaenoic acid (22:6(n − 3)) ester bonds was compared to that of oleic acid (18:1(n − 9)) or arachidonic acid (20:4(n − 6)) esters. As model substrates, we used rat chylomicrons obtained after feeding human milk fat globules and radiolabeled fatty acids. Radiolabeled chylomicrons were incubated with colipase-dependent pancreatic lipase, with BSSL, or with both enzymes in combination. Both enzymes hydrolyzed 18:1 more efficiently than 22:6 esters. With colipase-dependent lipase there was a large accumulation of 22:6 in diacylglycerol whereas with BSSL it accumulated mainly in monoacylglycerol. Esters containing 20:4 were hydrolyzed by BSSL as efficiently as 18:1 but this fatty acid also accumulated as diacylglycerol with colipase-dependent lipase. At low bile salt concentrations, as found in duodenal contents of newborns, colipase-dependent lipase was virtually unable to hydrolyze esters of 20:4 and 22:6 whereas BSSL hydrolyzed these esters at appreciable rates. Combining the two enzymes gave the most efficient hydrolysis of all fatty acids tested regardless of bile salt concentrations. BSSL may thus have a physiological role in completing duodenal hydrolysis of milk triacylglycerols containing 22:6- or 20:4-esters to free fatty acids and monoacylglycerol.
|
|
| 7. |
- Danielsson, Åke, et al.
(författare)
-
A controlled randomized trial of budesonide versus prednisolone retention enemas in active distal ulcerative colitis
- 1987
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 22:8, s. 987-992
-
Tidskriftsartikel (refereegranskat)abstract
- Sixty-four patients with active distal ulcerative colitis participated in a multicentre, randomized, investigator-blind trial to compare the effect of budesonide enema, 2 mg/100 ml, with prednisolone disodium phosphate enema, 31.25 mg/100 ml. Budesonide is a new potent corticosteroid with a rapid first-pass elimination. The patients were treated for 4 weeks, and the efficacy of the drugs were evaluated by sigmoidoscopy, histology, and subjective symptoms after 2 and 4 weeks. After 4 weeks of treatment 16 of 31 patients (52%) receiving budesonide enema had healed endoscopically, compared with 8 of 33 (24%) (p = 0.045) receiving prednisolone enema. Budesonide was superior to prednisolone in terms of both significantly improved sigmoidoscopic and histologic scores and subjective symptoms evaluated by visual analogue scales. The patients receiving prednisolone had a significant depression of endogenous cortisol levels during the treatment period, but not the patients receiving budesonide. Budesonide enema seems to be a promising therapy for active distal ulcerative colitis and causes no adverse reactions
|
|
| 8. |
- Duan, Rui-Dong, et al.
(författare)
-
Alkaliskt sfingomyelinas, en antiinflamatorisk faktor som kan motverka colit och colorektal cancer
- 2019
-
Ingår i: Gastrokuriren. - 1651-0453. ; 24:2, s. 26-27
-
Konferensbidrag (refereegranskat)abstract
- Alkaliskt sfingomyelinas, en antiinflammatorisk faktor som kan motverka colit och colorektal cancer Rui-Dong Duan, Erik Hertervig, Åke NilssonBakgrund: Borstbrämsenzymet alkaliskt sfingomyelinas (alk-SMas) som vi upptäckt, renat och klonat hydrolyserar sfingomyelin (SM) och den proinflammatoriska glycerofosfolipiden platelet activating factor (PAF). Metaboliter av SM är anticarcinogena och inaktivering av PAF är antiinflammatorisk. Alk-SMas nivån är sänkt vid coloncancer (CRC) (1), familjär colonpolypos och långvarig colit. Rektal administration av rekombinant alk-SMas lindrar experimentell colit och alk-SMas knockout (KO) möss är känsligare för induktion av colontumörer i en kombinerad colit/carcinogenmodell (2). Enzymet secerneras också i human galla och vi fann låga värden i ERCP galla från patienter med PSC och cholangiocarcinom. Alk-SMas KO möss utvecklar svårare dextransulfat colit än kontrollmöss (3). Metod: Vi analyserade PAF, enzymet autotaxin och dess metabolit lysofosfatidinsyra (LPA) i mucosan hos alk-SMas KO och kontrolldjur med colit inducerad med dextransulfat (3). Både PAF och LPA är trofiska och proinflammatoriska signalsubstanser. Fynden relaterades till colitens svårighetsgrad. Studien gav en mekanistisk bakgrund till alk-SMas anticarcinogena och antiinflammatoriska effekter. Vi kan därigenom bättre bedöma alk-SMas kliniska potential. Resultat: Vi fann att alk-SMas KO möss har högre PAF nivåer i mucosan under colitens induktionsfas och att nivån av autotaxin och LPA är högre i KO djuren när inflammationen etablerats (3). Bland våra tidigare fynd vill vi lyfta fram att alk-SMas uttryck kan nedregleras av fettrik kost, och ökas av lösliga fiber, 5-ASA och ursodeoxycholsyra. Slutsats: 1. Den anticarcinogena effekten av alk-SMas kan vara sekundär till den antiinflammatoriska effekten. 2. Reduktionen av på PAF och LPA nivåer är sannolikt viktigare för effekten än bildningen av sfingolipidmetaboliter. 3. Påverkan på alk-SMas nivån bidrar till kända effekter av kost och farmaka på inflammation och carcinogenes i colon. 4. Alk-SMas är proteasresistent och kan analyseras i faeces. 5 Alk SMase kan ges som slow release eller rektal beredning. Referenser: 1.Hertervig E, Nilsson A, Nyberg L, Duan RD. Alkaline sphingomyelinase activity is decreased in human colorectal carcinoma. Cancer. 1997; 79:448-53. 2. Chen Y, Zhang P, Xu SC, Yang L, Voss U, Ekblad E, Wu Y, Min Y, Hertervig E, Nilsson Å, Duan RD. Enhanced colonic tumorigenesis in alkaline sphingomyelinase (NPP7) knockout mice. Mol Cancer Ther. 2015; 14:259-67.3. Zhang P, Chen Y, Zhang T, Zhu J, Zhao L, Li J, Wang G, Li Y, Xu S, Nilsson Å, Duan RD. Deficiency of alkaline SMase enhances dextran sulfate-induced colitis in mice with upregulation of autotaxin. J Lipid Res. 2018; 59:1841-1850.
|
|
| 9. |
- Duan, Rui-Dong, et al.
(författare)
-
Changes of activity and isoforms of alkaline sphingomyelinase (nucleotide pyrophosphatase phosphodiesterase 7) in bile from patients undergoing endoscopic retrograde cholangiopancreatography.
- 2014
-
Ingår i: BMC Gastroenterology. - 1471-230X. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Alkaline sphingomyelinase (NPP7) is an ecto-enzyme expressed in intestinal mucosa, which hydrolyses sphingomyelin (SM) to ceramide and inactivates platelet activating factor. It is also expressed in human liver and released in the bile. The enzyme may have anti-tumour and anti-inflammatory effects in colon and its levels are decreased in patients with colon cancer and ulcerative colitis. Active NPP7 is translated from a transcript of 1.4 kb, whereas an inactive form from a 1.2 kb mRNA was found in colon and liver cancer cell lines. While the roles of NPP7 in colon cancer have been intensively studied, less is known about the function and implications of NPP7 in the bile. The present study examines the changes of NPP7 in bile of patients with various hepatobiliary diseases.
|
|
| 10. |
- Feng, Dan, et al.
(författare)
-
Generating Ceramide from Sphingomyelin by Alkaline Sphingomyelinase in the Gut Enhances Sphingomyelin-Induced Inhibition of Cholesterol Uptake in Caco-2 Cells.
- 2010
-
Ingår i: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 1573-2568 .- 0163-2116. ; Mar 4, s. 3377-3383
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Sphingomyelin (SM) is present in dietary products and cell plasma membranes. We previously showed that dietary SM inhibited cholesterol absorption in rats. In the intestinal tract, SM is mainly hydrolyzed by alkaline sphingomyelinase (alk-SMase) to ceramide. AIMS: We investigated the influence of SM and its hydrolytic products ceramide and sphingosine on cholesterol uptake in intestinal Caco-2 cells. METHODS: Micelles containing bile salt, monoolein, and (14)C-cholesterol were prepared with or without SM, ceramide, or sphingosine. The micelles were incubated with Caco-2 cells, and uptake of radioactive cholesterol was quantified. RESULTS: We found that confluent monolayer Caco-2 cells expressed NPC1L1, and the uptake of cholesterol in the cells was inhibited by ezetimibe, a specific inhibitor of NPC1L1. Incorporation of SM in the cholesterol micelles inhibited cholesterol uptake dose-dependently; 38% inhibition occurred at an equal mole ratio of SM and cholesterol. The inhibition was further enhanced to 45% by pretreating the cholesterol/SM micelles with recombinant alk-SMase, which hydrolyzed SM in the micelles by 85%, indicating ceramide has stronger inhibitory effects on cholesterol uptake. To confirm this, we further replaced SM in the micelles with ceramide and sphingosine, and found that at equal mole ratio to cholesterol, ceramide exhibited stronger inhibitory effect (50% vs 38%) on cholesterol uptake than SM, whereas sphingosine only had a weak effect at high concentrations. CONCLUSION: Both SM and ceramide inhibit cholesterol uptake, the effect of ceramide being stronger than that of SM. Alk-SMase enhances SM-induced inhibition of cholesterol uptake by generating ceramide in the intestinal lumen.
|
|
