| Title: | Histological analyses by matrix-assisted laser desorption/ionization-imaging mass spectrometry reveal differential localization of sphingomyelin molecular species regulated by particular ceramide synthase in mouse brains |
| Authors: | Sugimoto, Masayuki Browse this author |
| Shimizu, Yoichi Browse this author →KAKEN DB |
| Yoshioka, Takeshi Browse this author |
| Wakabayashi, Masato Browse this author |
| Tanaka, Yukari Browse this author |
| Higashino, Kenichi Browse this author |
| Numata, Yoshito Browse this author |
| Sakai, Shota Browse this author |
| Kihara, Akio Browse this author →KAKEN DB |
| Igarashi, Yasuyuld Browse this author |
| Kuge, Yuji Browse this author →KAKEN DB |
| Keywords: | Imaging mass spectrometry |
| Fourier transform ion cyclotron resonance |
| Sphingomyelin |
| Ceramide synthase |
| Very long-chain fatty acid |
| Issue Date: | Dec-2015 |
| Publisher: | Elsevier |
| Journal Title: | Biochimica et Biophysica Acta. Molecular and Cell Biology of Lipids |
| Volume: | 1851 |
| Issue: | 12 |
| Start Page: | 1554 |
| End Page: | 1565 |
| Publisher DOI: | 10.1016/j.bbalip.2015.09.004 |
| PMID: | 26398595 |
| Abstract: | Sphingomyelin (SM) is synthesized by SM synthase (SMS) from ceramide (Cer). SM regulates signaling pathways and maintains organ structure. SM comprises a sphingoid base and differing lengths of acyl-chains, but the importance of its various forms and regulatory synthases is not known. It has been reported that Cer synthase (CerS) has restricted substrate specificity, whereas SMS has no specificity for different lengths of acyl-chains. We hypothesized that the distribution of each SM molecular species was regulated by expression of the CerS family. Thus, we compared the distribution of SM species and CerS mRNA expression using molecular imaging. Spatial distribution of each SM molecular species was investigated using ultra-high-resolution imaging mass spectrometry (IMS). IMS revealed that distribution of SM molecular species varied according to the lengths of acyl-chains found in each brain section. Furthermore, a combination study using in situ hybridization and IMS revealed the spatial expression of CerS1 to be associated with the localization of SM (d18:1/18:0) in cell body-rich gray matter, and CerS2 to be associated with SM (d18:1/24:1) in myelin-rich white matter. Our study is the first comparison of spatial distribution between SM molecular species and CerS isoforms, and revealed their distinct association in the brain. These observations were demonstrated by suppression of CerS2 using siRNA in HepG2 cells; that is, siRNA for CerS2 specifically decreased C22 very long-chain fatty acid (VLCFA)- and C24 VLCFA-containing SMs. Thus, histological analyses of SM species by IMS could be a useful approach to consider their molecular function and regulative mechanism. |
| Rights: | © 2015. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/63713 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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