Important roles of heme-regulated eIF-2 alpha kinase in cadmium-induced glycolysis under acute exposure

Cadmium (Cd) is a well-known heavy metal pollutant that is a toxic threat to human health. Cadmium can induce anemia and is involved in metabolic disorders. Heme-regulated eIF2 alpha kinase (HRI) is the main regulator of terminal erythropoiesis and is required to prevent anemia and toxicity in the liver and kidneys in response to various stresses including Cd exposure. However, the involvement of HRI in Cd-induced metabolic disorders remains unclear. In this study, we performed proteomics on plasma collected from wild-type and Hri knockout mice treated with or without 5 and 10 mg/kg Cd. In total, 382 proteins were identified and indicated that the number of proteins in wild-type (Wt) mice was 2.4-fold higher than that in Hri knockout mice after Cd exposure, indicating the requirement of HRI for Cd exposure responses. Proteins associated with glycolysis were the most upregulated after Cd exposure in Wt mice, while, the induction of glycolysis after Cd exposure was interrupted in Hri knockout mice, suggesting the involvement of HRI in Cd-induced glycolysis upon acute exposure. Our results will help identify potential targets involved in metabolic disorders following acute exposure to high doses of cadmium.

Automated summary

Cadmium is a toxic heavy metal pollutant that can cause anemia and metabolic disorders. Heme-regulated eIF2 alpha kinase (HRI) plays a crucial role in preventing anemia and toxicity in response to various stresses, including cadmium exposure. This study identified proteins associated with glycolysis that were upregulated after cadmium exposure in wild-type mice, but this induction was disrupted in Hri knockout mice, suggesting the involvement of HRI in cadmium-induced glycolysis. These findings provide insights into potential targets for metabolic disorders following acute cadmium exposure.