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 b y hypotonic stress or a high glutamine uptake modulates the transcript ion of given genes in liver, This could be important in the acute phas e (AP) of a systemic inflammation where both HS and glutamine uptake t ransiently increase in liver, In HepG2 hepatoma cells cultured in cond itions of hypotonic stress or a high extracellular glutamine availabil ity, a specifically decreased expression of two human mRNAs, namely th ose of alpha 1-microglobulin/bikunin precursor (AMBP) and alpha 2-HS-g lycoprotein, that are also down-regulated in liver by AP, could be see n. A functional analysis of the AMBP promoter indicated that this hypo tonic stress-induced down-regulation takes place at a transcriptional level. In these experiments, the mRNA level and transcription of the g lyceraldehyde-3-phosphate dehydrogenase gene that are known to be unmo dified in AP did not exhibit any change. Given that hypotonic stress a lso upregulates the transcription of a liver gene that is also upregul ated in AP [Meisse et al, (1998) FEES Lett. 422, 346-348], the AP-asso ciated increase in hepatocellular HS now appears to participate in the transcriptional control of both sets of genes that are up- or down-re gulated in AP, (C) 1998 Federation of European Biochemical Societies.