HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 16/2/247    most recent 00088.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Wong, M. S. Articles by Kelleher, J. K. Search for Related Content PubMed PubMed Citation Articles by Wong, M. S. Articles by Kelleher, J. K.

Metabolic and transcriptional patterns accompanying glutamine depletion and repletion in mouse hepatoma cells: a model for physiological regulatory networks

¹ Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
² Bioinformatics and Pattern Discovery Group, IBM T. J. Watson Research Center, Yorktown Heights, New York 10598
³ Department of Physiology, George Washington University School of Medical and Health Sciences, Washington, District of Columbia 20037

An important objective in postgenomic biology is to link gene expression to function by developing physiological networks that include data from the genomic and functional levels. Here, we develop a model for the analysis of time-dependent changes in metabolites, fluxes, and gene expression in a hepatic model system. The experimental framework chosen was modulation of extracellular glutamine in confluent cultures of mouse Hepa1-6 cells. The importance of glutamine has been demonstrated previously in mammalian cell culture by precipitating metabolic shifts with glutamine depletion and repletion. Our protocol removed glutamine from the medium for 24 h and returned it for a second 24 h. Flux assays of glycolysis, the tricarboxylic acid (TCA) cycle, and lipogenesis were used at specified intervals. All of these fluxes declined in the absence of glutamine and were restored when glutamine was repleted. Isotopomer spectral analysis identified glucose and glutamine as equal sources of lipogenic carbon. Metabolite measurements of organic acids and amino acids indicated that most metabolites changed in parallel with the fluxes. Experiments with actinomycin D indicated that de novo mRNA synthesis was required for observed flux changes during the depletion/repletion of glutamine. Analysis of gene expression data from DNA microarrays revealed that many more genes were anticorrelated with the glycolytic flux and glutamine level than were correlated with these indicators. In conclusion, this model may be useful as a prototype physiological regulatory network where gene expression profiles are analyzed in concert with changes in cell function.

correlation; flux; microarray; carbon-13; carbon-14

This article has been cited by other articles:

				Y. Noguchi, N. Shikata, Y. Furuhata, T. Kimura, and M. Takahashi Characterization of dietary protein-dependent amino acid metabolism by linking free amino acids with transcriptional profiles through analysis of correlation Physiol Genomics, August 14, 2008; 34(3): 315 - 326. [Abstract] [Full Text] [PDF]

				M. Liang and B. Ventura Physiological genomics in PG and beyond: October to December 2005 Physiol Genomics, December 14, 2005; 24(1): 1 - 3. [Full Text] [PDF]

				J. D. Lee, W. I. Yang, Y. N. Park, K. S. Kim, J. S. Choi, M. Yun, D. Ko, T.-S. Kim, A. E.H. Cho, H. M. Kim, et al. Different Glucose Uptake and Glycolytic Mechanisms Between Hepatocellular Carcinoma and Intrahepatic Mass-Forming Cholangiocarcinoma with Increased 18F-FDG Uptake J. Nucl. Med., October 1, 2005; 46(10): 1753 - 1759. [Abstract] [Full Text] [PDF]