HEPATOCYTE SWELLING LEADS TO RAPID DECREASE OF THE G-ACTIN TOTAL ACTIN RATIO AND INCREASES ACTIN MESSENGER-RNA LEVELS

Exposure of isolated rat hepatocytes to hypotonic (190 mosmol/l) incubation media lowered the cellular G-actin level without affecting the total actin content: here the G-/total actin ratio decreased by 15.5 +/- 1.4% (n=7). Similar effects were observed following isotonic cell swelling by either addition of glutamine (10 mM) or insulin (100 nM), resulting in a decrease of the G-/total actin ratios by 13.5 +/- 2.1% (n = 5) and 14.1 +/- 1.1% (n = 11), respectively. The effects of hypotonic exposure, glutamine and insulin on the G-/total actin ratio largely occurred within 1 min and persisted for at least 2 h in presence of the respective effectors. After a 120 min exposure to hypotonic media, glutamine or insulin the actin mRNA levels were increased 2.4-, 2.0- and 3.6-fold, respectively. Hypertonic exposure lowered the G-/total actin ratio by only 4.9 +/- 2.5% (n = 4) and increased actin mRNA levels only 1.2-fold. There was a close relationship between glutamine- and hypotonicity-induced cell swelling and the decrease of G-/total actin ratios. The data suggest that cell swelling exerts rapid and marked effects on the state of actin polymerization and increases actin mRNA levels. Thus, cytoskeletal alterations in response to cell swelling may be involved in the regulation of hepatic metabolism by cell volume.