title: Moonlighting function of glycerol kinase causes systems-level changes in rat hepatoma cells.
abstract: Glycerol kinase (GK) is an enzyme with diverse (moonlighting) cellular functions. GK overexpression affects central metabolic fluxes substantially; therefore, to elucidate the mechanism underlying these changes, we employed a systems-level evaluation of GK overexpression in H4IIE rat hepatoma cells. Microarray analysis revealed altered expression of genes in metabolism (central carbon and lipid), which correlated with previous flux analysis, and of genes regulated by the glucocorticoid receptor (GR). Oil Red O staining showed that GK overexpression leads to increased fat storage in H4IIE cells. Network component analysis revealed that activities of peroxisome proliferator-activated receptor alpha, GR, and seven other transcription factors were altered by GK overexpression. The increased activity of GR was experimentally verified by quantitative RT-PCR of GR-responsive genes in the presence and absence of the glucocorticoid agonist, dexamethasone. This systems biology approach further emphasizes GK's essential role in central and lipid metabolism and experimentally verifies GK's alternative (moonlighting) function of affecting GR transcription factor activity.
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-7088, USA.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Sriram
authors.forename: Lilly S
authors.initials: LS
authors.lastname: Parr
authors.forename: Lola
authors.initials: L
authors.lastname: Rahib
authors.forename: James C
authors.initials: JC
authors.lastname: Liao
authors.forename: Katrina M
authors.initials: KM
authors.lastname: Dipple
mesh_terms: D000818:Animals; D002244:Carbon / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000378:metabolism; D005991:Glycerol Kinase; D050356:Lipid Metabolism; D047493:PPAR alpha / Q000378:metabolism; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D049490:Systems Biology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D047493:PPAR alpha; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; D002244:Carbon; D003907:Dexamethasone; C485945:Gk protein, rat; D005991:Glycerol Kinase
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