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Cholecystokinin (CCK) is known to rapidly and transiently increase both [Ca2+]iand autonomous CaM kinase II activity in rat pancreatic acini. Because induction of autonomous activity may involve intramolecular autophosphorylation, the effects of protein phosphatase inhibitors were examined. None of the inhibitors tested (okadaic acid, calyculin A, and cyclosporin A) affected basal activity. Okadai
The hydrolysis of sphingomyelin has been found to generate important signals regulating cell proliferation, differentiation and apoptosis. However, the enzymes responsible for digestion of dietary sphingomyelin have not been well documented. This study demonstrates the occurrence of a sphingomyelinase (SMase) in both human hepatic bile and gallbladder bile. The enzyme was equally found in both bac
Escherichia coli express fimbriae-associated adhesins through which they attach to mucosal cells and activate a cytokine response. The receptors for E. coli P fimbriae are the globoseries of glycosphingolipids; Gal alpha 1-->4Gal beta-containing oligosaccharides bound to ceramide in the outer leaflet of the lipid bilayer. The receptors for type 1 fimbriae are mannosylated glycoproteins rather than
By attaching to cells or secreted mucosal components, microbes are thought to avoid elimination by the flow of secretions that constantly wash mucosal surfaces. The attached state enhances their ability to trap nutrients and allows the bacteria to multiply more efficiently than do unattached bacterial cells. Attachment is therefore regarded as an end result in itself, and emphasis has been placed
The hydrolysis of sphingomyelin (SM) generates important signals regulating cell proliferation and apoptosis. Acid and neutral sphingomyelinases (SMase) have been identified and their biological effects intensively studied. We recently found in human bile a novel alkaline SMase that may have important roles in hepatobiliary diseases. In this work, we purified the enzyme and studied the factors inf
Dietary sphingomyelin (SM) undergoes sequential cleavage to ceramide and sphingosine in the intestine. A distinctive intestinal sphingomyelinase (SMase) with alkaline pH-optimum was earlier identified by us. The activity was highest in middle and lower small intestine, but its role in SM digestion has not been clarified. In this study we examined the extension and capacity of SM digestion in vivo.
BACKGROUNDThere is a renewed interest in metabolism of sphingolipids because of their role in signal transduction. Sphingomyelin is the dominating phospholipid in human milk but its metabolism and possible function in the gastrointestinal tract of breast fed infants is unknown. We explored whether bile salt-stimulated milk lipase has a role in sphingolipid metabolism.METHODSIn vitro assays of sphi
Two studies were conducted to investigate the role of meat and arachidonic acid in colonie signal transduction, particularly protein kinase C (PKC) activation. In Study 1, 26 male Wistar rats were fed a casein‐ or a beef‐based diet for four weeks. PKC activity was measured from the proximal and distal colonie mucosa and diacylglycerol concentration from fecal samples. The beef diet significantly i
Uropathogenic Escherichia coli attach to epithelial cells through P fimbriae that bind Galα1‐4Galβ‐oligosaccharide sequences in cell surface glycosphingolipids. The binding of P‐fimbriated E. coli to uroepithelial cells causes the release of ceramide, activation of the ceramide signalling pathway and a cytokine response in the epithelial cells. The present study examined the molecular source of ce
Previous studies showed that bile salts had apromoting effect on colon cancer development and thiseffect was inhibited by ursodeoxycholate (UDC). Werecently found that both human colorectal adenomas and carcinomas were associated with a specificdecrease in alkaline sphingomyelinase activity. In thiswork, we compared the effects of ursodeoxycholate andother bile salts on the levels of rat intestina
BACKGROUND:Ursodeoxycholic acid (UDCA) has been found to inhibit the development of colon carcinoma induced by chemical carcinogens with unidentified mechanisms. Sphingomyelin metabolism has emerged as a novel signal transduction pathway closely related to cell proliferation and apoptosis. We recently found that alkaline sphingomyelinase (SMase) activity was decreased in human colon cancer. The pr
In the intestinal tract, there are enzymes that hydrolyze both endogenous and exogenous sphingolipids. The alkaline sphingomyelinases (SMase) of the gut and human bile have been most studied, and a major part of this chapter discusses these enzymes. It also discusses studies of ceramidase, glycosylceramidase, and the digestion of dietary sphingolipids. In the intestinal tract, a distinct enzyme th
We recently reported that a red meat (beef) diet relative to a casein-based diet increases protein kinase C (PKC) activity in rat colonic mucosa. The purpose of this study was to further elucidate the effects of a high-beef diet on colonic intracellular signal transduction by analyzing steady-state protein levels of different PKC isozymes as well as activities of the three types of sphingomyelinas
Several studies have shown that there is a strong physical interaction between cholesterol and sphingomyelin (SM). The critical factor is thought to be the high degree of saturation in the very long acyl chains of SM. In this study we examined the effects of SM on cholesterol absorption in the rat and compared them with those of phosphatidylcholine (PC). Cholesterol absorption was studied by use o
