Effects of acidosis on acute phase protein metabolism in liver cells

Metabolic acidosis has been shown to act as a causative factor in muscle protein breakdown and negative nitrogen balance, as well as in decreased albumin synthesis. Albumin and other acute phase proteins (APP) are mainly synthesized in the liver following induction by interleukins, hormones and other mediators. Acute phase proteins have been shown to be predictors of cardiovascular mortality in the general population and in patients with end stage renal disease (ESRD). Clinical investigation gives evidence that albumin is reduced by acidosis in ESRD patients. The aim of our study was to investigate the role of the liver in acidosis, i.e. the influence of acidosis on metabolic activity and secretion of APP by liver cells (HepG2). Cells were cultured in a medium containing different amounts of bicarbonate. Metabolic activity was significantly diminished when the bicarbonate concentration of the extracellular medium was reduced (86.13+/-1.90% (pH 7.0) vs. 99. 53+/-90% (pH 7.4); p<0.01). While cellular release of negative APP was significantly decreased (albumin: 4.6+/-0.41 (pH 7.0) vs. 7.54+/-0.62 (pH 7.4) [ng/microg protein], p<0.001, transferrin: (0. 78+/-0.08 (pH 7.0) vs. 1.07+/-0.07 (pH 7.4) [ng/microg protein], p<0. 05), no significant influence of acidosis (pH 7.0) on the positive APP, alpha(1)-acid glycoprotein (AGP) (1.69+/-0.25) (pH 7.0) vs. 1.62+/-0.23 (pH 7.4) [ng/microg protein]), could be shown. Our data indicate that acidosis results in inhibition of liver cell metabolic activity and in reduced secretion of the negative acute phase proteins albumin and transferrin. In contrast, secretion of the positive acute phase protein AGP seems to be unchanged at pH 7.0 as compared to pH 7.4. We conclude that negative and positive APP in liver cells (HepG2) appear to be differently regulated by acidosis.