title: Temporal expression profiles of ceramide and ceramide-related genes in wild-type and mPer1/mPer2 double knockout mice.
abstract: Most living organisms exhibit circadian rhythms in physiology and behavior. These oscillations are generated by an endogenous circadian clock and control many biological processes. Ceramide has attracted attention as a signal mediator in diverse cell processes including cell death and differentiation. The relationships between ceramide expression levels and the circadian clock have not previously been investigated. To determine if there are circadian variations in the content of ceramide, we measured ceramide concentrations in the livers of wild-type (WT) and mPer1/mPer2 double knockout (DKO) mice. The ceramide concentration in WT mice was dramatically increased at Zeitgeber Time 9 (ZT9; 9 h after lights-on time) and ZT21 but no rhythmicity in ceramide expression was seen in DKO mice. Because ceramide can be generated by the hydrolysis of sphingomyelin via sphingomyelinase (SMase), or by ceramide synthase (CerS)-mediated synthesis, we assayed the expression patterns of ceramide-related genes using real-time PCR. CerS2 expression levels showed a biphasic pattern of expression in WT mice but no rhythmicity in DKO mice. While the neutral SMase (nSMase) and acidic SMase (aSMase) mRNA in WT mice were expressed in a circadian manner, the correlation between the expression levels of these SMases with times of day was weak in DKO mice. Collectively, our findings suggest that both SMases and CerS2 mRNA expression are regulated by the presence of mPer1/mPer2 circadian clock genes in vivo, and imply that ceramide may play a vital role in circadian rhythms and physiology.
authors.affiliation: Division of Biological Science and Technology, College of Science and Technology, Yonsei University, 1 Yonseidae-gil, Wonju, 220-710, Republic of Korea.
authors.forename: Yeong-Su
authors.initials: YS
authors.lastname: Jang
authors.forename: Yeo-Jin
authors.initials: YJ
authors.lastname: Kang
authors.forename: Tack-Joong
authors.initials: TJ
authors.lastname: Kim
authors.forename: Kiho
authors.initials: K
authors.lastname: Bae
mesh_terms: D000818:Animals; D002518:Ceramides / Q000378:metabolism*; D002940:Circadian Rhythm / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D056950:Period Circadian Proteins / Q000172:deficiency* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics / Q000378:metabolism; D051049:Sphingosine N-Acyltransferase / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D002518:Ceramides; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D051049:Sphingosine N-Acyltransferase; D013108:Sphingomyelin Phosphodiesterase