Effect of glucocorticoids and extracellular pH on protein metabolism in cultured cells

Chronic renal failure (CRF) is complicated by metabolic acidosis and muscle wasting. Protein degradation (PD) in skeletal muscle is accelerated in rats with CRF and correction of uremic acidosis returns PD to normal. Experimentally induced acidosis in normal rats accelerates PD and requires an intact adrenal axis. To investigate mechanisms of pH-induced changes in protein metabolism, BC3Hl myocytes and LLC-PK1 renal epithelial cells were studied. Low extracellular pH increases PD in myocytes but does not change PD in LLC-PK1 cells. In both types of cells, intracellular pH changes predictably as extracellular pH is varied. Exogenous glucocorticoids (GC) do not alter PD in either cell line, but inhibit protein synthesis in BC3Hl myocytes. Since extracellular pH stimulates PD only in BC3Hl myocytes and since LLC-PK1 cells may not possess GC receptors, we can compare and contrast the effects of pH and GC on protein metabolism to study the role of GC in acid-stimulated proteolysis.