Down-regulation of negative acute-phase response genes by hypotonic stress in HepG2 hepatoma cells

• Published in: FEBS letters Vol. 433; no. 1; pp. 15 - 18
• Main Authors: Claeyssens, Sophie, Banine, Fatima, Rouet, Philippe, Lavoinne, Alain, Salier, Jean-Philippe
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 14.08.1998
• Subjects: Acute-phase gene; Acute-Phase Reaction - genetics; AHSG, α2-HS-glycoprotein; alpha-2-HS-Glycoprotein; Alpha-Globulins - genetics; AMBP, α1-microglobulin/bikunin precursor; AP, acute phase; APP, acute-phase protein; AR, aldose reductase; Blood Proteins - genetics; BT, betaine transporter; Carcinoma, Hepatocellular - genetics; Cat, chloramphenicol acetyltransferase; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; Gene Expression Regulation, Neoplastic; Glutamine; Glutamine - administration & dosage; Glyceraldehyde-3-Phosphate Dehydrogenases - genetics; Glycoproteins - genetics; Hepatoma cell; HS, hydration state; Humans; Hydration state; hypo, hypotonic medium; Hypotonic Solutions; iso, isotonic medium; isoraff, raffinose-supplemented, isotonic medium; Liver Neoplasms - genetics; Membrane Glycoproteins; PEPCK, phosphoenolpyruvate carboxykinase; Promoter Regions, Genetic; Protein Precursors - genetics; RNA, Messenger - metabolism; Serine Proteinase Inhibitors - genetics; tk, thymidine kinase; Transcriptional regulation; Trypsin Inhibitor, Kunitz Soybean; Tumor Cells, Cultured; α2-M, α2-macroglobulin; β-gal, β-galactosidase; Acute-phase gene; BT, betaine transporter; Cat, chloramphenicol acetyltransferase; PEPCK, phosphoenolpyruvate carboxykinase; Transcriptional regulation; AR, aldose reductase; tk, thymidine kinase; Hydration state; Hepatoma cell; β-gal, β-galactosidase; hypo, hypotonic medium; APP, acute-phase protein; α2-M, α2-macroglobulin; HS, hydration state; iso, isotonic medium; isoraff, raffinose-supplemented, isotonic medium; AHSG, α2-HS-glycoprotein; AMBP, α1-microglobulin/bikunin precursor; AP, acute phase; Glutamine; GAPDH, glyceraldehyde-3-phosphate dehydrogenase
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(98)00868-0

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 α1-microglobulin/bikunin precursor (AMBP) and α2-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 up-regulates the transcription of a liver gene that is also up-regulated in AP [Meisse et al. (1998) FEBS Lett. 422, 346–348], 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.