GENE-EXPRESSION OF IRON-RELATED PROTEINS DURING IRON-DEFICIENCY CAUSED BY SCURVY IN GUINEA-PIGS

The regulation of expression of hepatic iron-related proteins was exam ined during iron deficiency caused by scurvy in guinea pigs. Previous studies showed that some effects of scurvy, such as suppression of col lagen gene expression, result from events associated with weight loss. During the initial phase of scurvy when vitamin C is depleted but ani mals grow normally, serum iron levels decreased to 50% of normal. Duri ng the second phase of scurvy when animals lose weight, there was a fu rther decrease in iron levels to 10-15% of normal. Serum transferrin l evels increased during scurvy, but this increase was related neither t o the rate of weight loss nor to hepatic transferrin mRNA expression, which decreased. Serum ferritin levels diminished early in scurvy with a preferential loss of the L subunit. In liver, however, both ferriti n subunits were almost undetectable even in scorbutic animals gaining weight. Ferritin gene expression during vitamin C deficiency was corre lated with serum ferritin levels in that the level of mRNA for the H s ubunit remained relatively constant while that of the L subunit decrea sed early. Transferrin receptor mRNA expression in liver was induced a s soon as iron levels decreased early in scurvy, which is similar to r esults reported for iron-depleted cultured cells. In contrast to resul ts in cell culture, expression of iron regulatory protein 1 mRNA was d ecreased to approximately 50% of normal early in scurvy with a concomi tant decrease in hepatic cytosolic aconitase activity. Our data indica te that iron deficiency occurs early during vitamin C deficiency and l eads to changes in expression of iron-related proteins that differ in some aspects from regulation by iron in cell culture. Other events ass ociated with weight loss in late scurvy may play a further role in thi s regulation. (C) 1996 Academic Press, Inc.