Distribution of alkaline sphingomyelinase activity in human beings and animals

Abstract

The alkaline sphingomyelinase (SMase) was first found in rat intestinal brush border. The important roles of this enzyme in digestion of sphingomyelin and in mucosal cell proliferation have been suggested. In the present work, the distribution of the alkaline SMase in the tissues of human beings and animals have been studied. By assaying the enzyme activity in human biopsy samples, we found that the alkaline SMase activity was absent in the stomach, increased in the duodenum, present at high levels in the small intestine, and slightly declined in the colon and rectum. High activities were found similarly in the intestinal contents of the healthy adults and infants. The activities were also found in the intestinal mucosa of rats, normal and germ-free mice, and hamsters with the same distribution pattern as in humans, but not in the intestinal mucosa of guinea pigs. Apart from the intestinal tract, a SMase activity preferring alkaline pH was identified in human and guinea pig bile, but not in the bile of rat, pig, sheep, and cow. No activity was found in either pancreatic tissue or pancreatic juice in all species tested, and none was detected in human urine and milk. In conclusion, alkaline SMase exists predominantly in the digestive system with considerable tissue and species differences.

Effects of bile diversion in rats on intestinal sphingomyelinases and ceramidase

“…The effect is more potent on differentiated enterocytes than on proliferating cells. Another interesting feature of Alk-SMase is its biliary secretion in humans but not in other species, as convinced by activity assay, Western blot and Northern blot in our previous studies [3,4,18,19]. Bile salt dependent hydrolysis of SM in the gut lumen or in the brush border membrane may indirectly influence cholesterol absorption [20], which is highly dependent on bile salts.…”

“…Experimental protocols were approved by the Ethical Committee for Animal Experiments, Faculty of Medical Sciences, University of Groningen. One group of rats (n=4) were equipped with permanent catheters at the proximal common bile duct (bile-deficiency rats) and the bile was continuously drained (19). Animals were allowed to recover from surgery for 1 week, after which they were subjected to overnight fasting.…”

Familial adenomatous polyposis is associated with a marked decrease in alkaline sphingomyelinase activity: A key factor to the unrestrained cell proliferation?

“…The activity of alkaline SMase was determined according to Duan et al (1995aDuan et al ( , 1995b which is a modification of an original method for neutral SMase (Gatt, 1975). Briefly, samples were added in 375 µl Tris-EDTA buffer pH 9.0 to a final volume of 0.4 ml, containing 50 mM Tris, 0.15 M sodium chloride (NaCl), 2 mM EDTA and 3 mM bile salt mixture with a molar ratio TC:TDC:GC:GCDC being 3:2:1.8:1.…”

“…The first two, termed acid and neutral SMase respectively, have been found in many tissues and are considered as common cellular enzymes (Chatterjee, 1994;Spence, 1994). The third enzyme, alkaline SMase, has been located specifically to the intestinal tract, where high levels are found in the small intestine and lower in the colon with a gradual decline towards rectum (Nilsson, 1969;Duan et al, 1995aDuan et al, , 1995b. This enzyme may play an important role in the digestion of dietary SM and provide the intestinal mucosa with ceramide, a key molecule to induce apoptosis (Obeid et al, 1993).…”

Generating Ceramide from Sphingomyelin by Alkaline Sphingomyelinase in the Gut Enhances Sphingomyelin-Induced Inhibition of Cholesterol Uptake in Caco-2 Cells

“…The enzyme is specifically expressed in the intestinal tract and human liver and is at high levels in the middle of small intestine [11]. Alk-SMase shares no structural similarities with other SMases, and belongs to nucleotide pyrophosphatase phosphodiesterase (NPP) family, and is therefore also called NPP7 [12].…”