Analysis of hepatic transferrin receptor‐1 (TFR1) demonstrates appropriate iron‐sensing in old rats after environmental heat stress

Abstract

Elevations in hepatic iron content occur with aging and physiological stressors, which may promote oxidative injury to the liver. The cellular mechanism for this increase in iron is unclear, but may involve differential regulation of iron import proteins. Transferrin receptor‐1 (TFR1) facilitates iron influx by binding diferric transferrin, while divalent metal ion transporter‐1 (DMT1) is thought to mediate influx of non‐transferrin‐bound iron. The purpose of this study was to evaluate a role for these iron transport proteins in the transient increase in hepatic iron after heat stress in old rats. Young (6 mo) and old (24 mo) Fischer 344 rats underwent a two‐heat stress protocol and livers were harvested at 0, 2, and 24 h after the second heat stress. Immunoblot analysis was utilized to evaluate the expression TFR1 and DMT1. Under control conditions, expression of both TFR1 and DMT1 was significantly lower in old, compared to young rats. After heat stress, TFR1 declined in the old rats, but was unchanged in the young cohort. Hyperthermia did not affect expression of DMT1 in either age group. Since TFR1 is inversely regulated by intracellular iron, these results demonstrate that after heat stress, old rats mount an appropriate response to an increase in hepatic iron. The results also suggest that TFR1 is sensitive to acute changes in iron, while DMT1 seems responsive only to more chronic changes in hepatic iron content.