title: Analysis of the Involvement of Different Ceramide Variants in the Response to Hydroxyurea Stress in Baker's Yeast.
abstract: Sphingolipids have been identified as important signaling compounds in stress responses. However, it is not always clear how different sphingolipid profiles are achieved in a particular stress situation. Here we propose a detailed mass action model, containing 42 dependent variables and 137 reactions, that offers explanations of the roles of variant ceramides species, which differ in the lengths of their fatty acyl chains and their saturation state, in the response to hydroxyurea stress. The simulations demonstrate that the cells manage to achieve hydroxyurea tolerance through a well-coordinated, differential usage of the variant ceramide species. Moreover, the results suggest that key enzymes have different affinities toward saturated and unsaturated fatty acyl chains, which implies that the saturation state affords the cells with an additional mode of regulation that had not been recognized so far. These conclusions from our computational analysis are yet to be validated experimentally.
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States of America.|The George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States of America.
authors.forename: Po-Wei
authors.initials: PW
authors.lastname: Chen
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States of America.
authors.forename: Luis L
authors.initials: LL
authors.lastname: Fonseca
authors.affiliation: The Cancer Center at Stony Brook Medicine, Stony Brook University, Health Science Center, Stony Brook, New York, United States of America.
authors.forename: Yusuf A
authors.initials: YA
authors.lastname: Hannun
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States of America.
authors.forename: Eberhard O
authors.initials: EO
authors.lastname: Voit
mesh_terms: D002518:Ceramides / Q000096:biosynthesis / Q000378:metabolism*; D006918:Hydroxyurea / Q000633:toxicity; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D002518:Ceramides; D006918:Hydroxyurea