Abstract

application) This core will measure tissue, cellular, and mitochondrial levels of ceramide, sphingosine, sphingosine-1-phosphate (S-1-P), diacylglycerol (DAG), and other lipids involved in the regulation of apoptosis. The core will concentrate mostly on the quantitative determination of total ceramide and DAG via DAG-kinase phosphorylation. In selected situations, LC-MS spectroscopic method will be used to obtain both qualitative and quantitative determination of the molecular species of ceramides present in specimens. Determination of the cellular levels of D-erythro-sphingosine and D-erythro-dihydrosphingosine will be based on the BPLC technique developed for their fluorescent analogs. A Synthetic Unit will provide homogenous sphingolipid standards corresponding to the naturally occurring lipids. This core will also synthesize radiolabeled analogs, which will allow the study of sphingolipid metabolic pathways. Key molecules to be synthesized include: stereoisomers of sphingosine, dihydrosphingosine, ceramides, dihydroceramide, sphingosine-1-phosphate and their modified analogs. Also, the core will provide inhibitors of sphingolipid metabolic pathways (e.g., D-e-MAPP).

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
1P01DK059340-01
Application #
6357656
Study Section
Special Emphasis Panel (ZDK1)
Project Start
2000-12-01
Project End
2005-11-30
Budget Start
Budget End
Support Year
1
Fiscal Year
2001
Total Cost
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Dolganiuc, Angela; Thomes, Paul G; Ding, Wen-Xing et al. (2012) Autophagy in alcohol-induced liver diseases. Alcohol Clin Exp Res 36:1301-8
Kim, Insil; Lemasters, John J (2011) Mitochondrial degradation by autophagy (mitophagy) in GFP-LC3 transgenic hepatocytes during nutrient deprivation. Am J Physiol Cell Physiol 300:C308-17
Kim, Insil; Lemasters, John J (2011) Mitophagy selectively degrades individual damaged mitochondria after photoirradiation. Antioxid Redox Signal 14:1919-28
Rodriguez-Enriquez, Sara; Kai, Yoichiro; Maldonado, Eduardo et al. (2009) Roles of mitophagy and the mitochondrial permeability transition in remodeling of cultured rat hepatocytes. Autophagy 5:1099-106
Kim, Insil; Rodriguez-Enriquez, Sara; Lemasters, John J (2007) Selective degradation of mitochondria by mitophagy. Arch Biochem Biophys 462:245-53
Adachi, Masayuki; Osawa, Yosuke; Uchinami, Hiroshi et al. (2007) The forkhead transcription factor FoxO1 regulates proliferation and transdifferentiation of hepatic stellate cells. Gastroenterology 132:1434-46
Lemasters, John J (2007) Modulation of mitochondrial membrane permeability in pathogenesis, autophagy and control of metabolism. J Gastroenterol Hepatol 22 Suppl 1:S31-7
Hammond, Linda E; Albright, Craig D; He, Lihua et al. (2007) Increased oxidative stress is associated with balanced increases in hepatocyte apoptosis and proliferation in glycerol-3-phosphate acyltransferase-1 deficient mice. Exp Mol Pathol 82:210-9
Osawa, Yosuke; Seki, Ekihiro; Adachi, Masayuki et al. (2006) Systemic mediators induce fibrogenic effects in normal liver after partial bile duct ligation. Liver Int 26:1138-47
Kono, Mari; Dreier, Jennifer L; Ellis, Jessica M et al. (2006) Neutral ceramidase encoded by the Asah2 gene is essential for the intestinal degradation of sphingolipids. J Biol Chem 281:7324-31

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