Crucial role of alkaline sphingomyelinase in sphingomyelin digestion: a study on enzyme knockout mice

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Yao Zhang, Yajun Cheng, Gert H Hansen, Lise-Lotte Niels-Christiansen, Frank Koentgen, Lena Ohlsson, Ake Nilsson, Rui-Dong Duan

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.
OriginalsprogEngelsk
TidsskriftJournal of Lipid Research
Vol/bind52
Udgave nummer4
Sider (fra-til)771-81
Antal sider11
ISSN0022-2275
DOI
StatusUdgivet - 1 apr. 2011

ID: 33544178