title: Crucial role of alkaline sphingomyelinase in sphingomyelin digestion: a study on enzyme knockout mice.
abstract: Alkaline sphingomyelinase (alk-SMase) hydrolyses sphingomyelin (SM) to ceramide in the gut. To evaluate the physiological importance of the enzyme, we generated alk-SMase knockout (KO) mice by the Cre-recombinase-Locus of X-over P1(Cre-LoxP) system and studied SM digestion. Both wild-type (WT) and KO mice were fed ³H-palmitic acid labeled SM together with milk SM by gavage. The lipids in intestinal content, intestinal tissues, serum, and liver were analyzed by TLC. In KO mice, nondigested ³H-SM in the intestinal content increased by 6-fold and the formation of ³H-ceramide decreased markedly, resulting in 98% reduction of ³H-ceramide/³H-SM ratio 1 h after gavage. The absorbed ³H-palmitic acid portion was decreased by 95%. After 3 h, a small increase in ³H-ceramide was identified in distal intestine in KO mice. In feces, ³H-SM was increased by 243% and ceramide decreased by 74% in the KO mice. The KO mice also showed significantly decreased radioactivity in liver and serum. Furthermore, alkaline phosphatase activity in the mucosa was reduced by 50% and histological comparison of two female littermates preliminarily suggested mucosal hypertrophy in KO mice. This study provides definite proof for crucial roles of alk-SMase in SM digestion and points to possible roles in regulating mucosal growth and alkaline phosphatase function.
authors.affiliation: Gastroenterology and Nutrition Laboratory, Biomedical Center B11, Lund University, S-221 84 Lund, Sweden.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yajun
authors.initials: Y
authors.lastname: Cheng
authors.forename: Gert H
authors.initials: GH
authors.lastname: Hansen
authors.forename: Lise-Lotte
authors.initials: LL
authors.lastname: Niels-Christiansen
authors.forename: Frank
authors.initials: F
authors.lastname: Koentgen
authors.forename: Lena
authors.initials: L
authors.lastname: Ohlsson
authors.forename: Ake
authors.initials: A
authors.lastname: Nilsson
authors.forename: Rui-Dong
authors.initials: RD
authors.lastname: Duan
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D005260:Female; D005838:Genotype; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics / Q000378:metabolism*; D013109:Sphingomyelins / Q000378:metabolism*
chemical_list: D013109:Sphingomyelins; D000469:Alkaline Phosphatase; D013108:Sphingomyelin Phosphodiesterase