Down-regulation of negative acute-phase response genes by hypotonic stress in HepG2 hepatoma cells.
An increased hepatocellular hydration state (HS) that can be induced by hypotonic stress or a high glutamine uptake modulates the transcription of given genes in liver. This could be important in the acute phase (AP) of a systemic inflammation where both HS and glutamine uptake transiently increase in liver. In HepG2 hepatoma cells cultured in conditions of hypotonic stress or a high extracellular glutamine availability, a specifically decreased expression of two human mRNAs, namely those of alphal-microglobulin/bikunin precursor (AMBP) and alpha2-HS-glycoprotein, that are also down-regulated in liver by AP, could be seen. A functional analysis of the AMBP promoter indicated that this hypotonic stress-induced down-regulation takes place at a transcriptional level. In these experiments, the mRNA level and transcription of the glyceraldehyde-3-phosphate dehydrogenase gene that are known to be unmodified in AP did not exhibit any change. Given that hypotonic stress also upregulates the transcription of a liver gene that is also upregulated in AP [Meisse et al. (1998) FEBS Lett. 422, 3463481, the AP-associated increase in hepatocellular HS now appears to participate in the transcriptional control of both sets of genes that are up- or down-regulated in AP.
Claeyssens
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S
Groupe de Biochimie et Physiopathologie Digestive et Nutritionnelle, Institut Fédératif de Recherches Multidisciplinaires sur les Peptides No. 23, Faculté de Médecine-Pharmacie, Rouen, France.
Banine
F
F
Rouet
P
P
Lavoinne
A
A
Salier
J P
JP
D000210:Acute-Phase Reaction / Q000235:genetics*; D000510:Alpha-Globulins / Q000235:genetics; D001798:Blood Proteins / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005973:Glutamine / Q000008:administration & dosage; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D007038:Hypotonic Solutions; D008113:Liver Neoplasms / Q000235:genetics*; D008562:Membrane Glycoproteins; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000235:genetics; D014360:Trypsin Inhibitor, Kunitz Soybean; D014407:Tumor Cells, Cultured; D060749:alpha-2-HS-Glycoprotein
C556354:AHSG protein, human; D000510:Alpha-Globulins; D001798:Blood Proteins; D006023:Glycoproteins; D007038:Hypotonic Solutions; D008562:Membrane Glycoproteins; D011498:Protein Precursors; D012333:RNA, Messenger; C109148:SPINT2 protein, human; D015842:Serine Proteinase Inhibitors; C016001:alpha-1-microglobulin; D060749:alpha-2-HS-Glycoprotein; D005973:Glutamine; D014360:Trypsin Inhibitor, Kunitz Soybean; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases