Sphingolipid Biology And Disease

鞘脂生物学与疾病

• 批准号: 7337498
• 负责人: RICHARD L. PROIA
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7337498
• 关键词: Sphingolipid; Biology; Disease

Sphingolipids are key mediators and regulators of cell signaling pathways. Our studies have focused on the actions of two classes of sphingolipids represented by glycosphingolipids (GSLs) and sphingosine-1-phosphate (S1P). Our work is aimed at defining the normal functions of these sphingolipids and understanding their roles in disease processes. Ceramidases are key enzymes in the regulation of the cellular levels of ceramide, sphingosine, and S1P.To explore the physiological functions of ceramidases, we disrupted the gene encoding neutral ceramidase (Asah2) in mice. Asah2 null mice have a normal life span and do not show obvious abnormalities or major alterations in total ceramide levels in tissues. The Asah2-encoded neutral ceramidase is highly expressed in the small intestine along the brush border, suggesting that the neutral ceramidase may be involved in a pathway for the digestion of dietary sphingolipids. Indeed, Asah2 null mice were deficient in the intestinal degradation of ceramide. Thus, the results indicate that the Asah2-encoded neutral ceramidase is a key enzyme for the catabolism of dietary sphingolipids and regulates the levels of bioactive sphingolipid metabolites in the intestinal tract. We are currently utilizing the Asah2 null mice to determine if defective catabolism of sphingolipids alters the growth of intestinal tumors.

鞘脂是细胞信号通路的关键介质和调节剂。我们的研究主要集中在鞘脂糖（GSLs）和鞘脂苷-1-磷酸（S1P）两类鞘脂的作用上。我们的工作旨在确定这些鞘脂的正常功能，并了解它们在疾病过程中的作用。

项目成果

Binding of soluble myelin-associated glycoprotein to specific gangliosides induces the association of p75NTR to lipid rafts and signal transduction

• DOI: 10.1111/j.1471-4159.2005.03121.x
• 发表时间: 2005-07-01
• 期刊: JOURNAL OF NEUROCHEMISTRY
• 影响因子: 4.7
• 作者: Fujitani, M;Kawai, H;Yamashita, T
• 通讯作者: Yamashita, T

Global gene expression in a type 2 Gaucher disease brain.

2 型戈谢病大脑中的整体基因表达。

• DOI: 10.1016/j.ymgme.2004.06.020
• 发表时间: 2004
• 期刊: Molecular genetics and metabolism
• 影响因子: 3.8
• 作者: Myerowitz,Rachel;Mizukami,Hiroki;Richardson,KristineL;Finn,LauraS;Tifft,CynthiaJ;Proia,RichardL
• 通讯作者: Proia,RichardL

Blood to brain to the rescue.

血液注入大脑来救援。

• DOI: 10.1172/jci21476
• 发表时间: 2004
• 期刊: The Journal of clinical investigation
• 作者: Proia,RichardL;Wu,Yun-Ping
• 通讯作者: Wu,Yun-Ping

Novel class of glycosphingolipids involved in male fertility.

参与男性生育能力的新型鞘糖脂。

• 发表时间: 2005
• 期刊: Journal of Biological Chemistry 280
• 作者: Iwamori M.Tanaka K.Kubushiro K.Lin B.Kiguchi K.Ishiwata I.Tsukazaki K.Nozawa;Iwamori M.Suzuki H.Ito N.Iwamori Y.Hanaoka K.;Sandhoff R.Geyer R.Jennemann R.Paret C.Kiss E.Yamashita T.Gorgas K.Sijmonsma TP.Iwamori M.Finaz C.Proia RL.Wiegandt H.Grone HJ.
• 通讯作者: Sandhoff R.Geyer R.Jennemann R.Paret C.Kiss E.Yamashita T.Gorgas K.Sijmonsma TP.Iwamori M.Finaz C.Proia RL.Wiegandt H.Grone HJ.

Interruption of ganglioside synthesis produces central nervous system degeneration and altered axon-glial interactions.

神经节苷脂合成的中断会导致中枢神经系统变性并改变轴突-神经胶质相互作用。

• DOI: 10.1073/pnas.0407785102
• 发表时间: 2005
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Yamashita,Tadashi;Wu,Yun-Ping;Sandhoff,Roger;Werth,Norbert;Mizukami,Hiroki;Ellis,JessicaM;Dupree,JeffreyL;Geyer,Rudolf;Sandhoff,Konrad;Proia,RichardL
• 通讯作者: Proia,RichardL