| First Author | Zhang Y | Year | 2011 |
| Journal | J Lipid Res | Volume | 52 |
| Issue | 4 | Pages | 771-81 |
| PubMed ID | 21177474 | Mgi Jnum | J:170667 |
| Mgi Id | MGI:4947032 | Doi | 10.1194/jlr.M012880 |
| Citation | Zhang Y, et al. (2011) Crucial role of alkaline sphingomyelinase in sphingomyelin digestion: a study on enzyme knockout mice. J Lipid Res 52(4):771-81 |
| abstractText | 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 (3)H-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 (3)H-SM in the intestinal content increased by 6-fold and the formation of (3)H-ceramide decreased markedly, resulting in 98% reduction of (3)H-ceramide/(3)H-SM ratio 1 h after gavage. The absorbed (3)H-palmitic acid portion was decreased by 95%. After 3 h, a small increase in (3)H-ceramide was identified in distal intestine in KO mice. In feces, (3)H-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. |
