Expression of ferroportin1, hephaestin and ceruloplasmin in rat heart

Abstract

Iron-mediated injury plays an important role in a number of heart disorders. Studies on heart iron are therefore crucial for understanding the causes of excessive heart iron. Heart cells have the ability to accumulate transferrin-bound-iron via the transferrin receptor and non-transferrin-bound-iron probably via the L-type Ca2+ channel and the divalent metal transporter1. However, little is known about the mechanisms of iron export in the heart cells. Here, we investigated expression of iron exporters including ferroportin 1 (Fpn1), ceruloplasmin (CP) and hephaestin (Heph) and provided evidence for their existence in the heart. We demonstrated that iron has a significant effect on expression of Fpn1 and CP, but not Heph. Treatment of a high-iron diet induced a significant increase in Fpn1, a decrease in CP but no change in Heph mRNA and protein. The control of Fpn1 and CP protein expression by iron was parallel to that of their mRNA expression, suggesting a transcriptional regulation of Fpn1 and CP by iron. The existence of these proteins in the heart implies that they might have a role in heart iron homeostasis.

Age-related changes in iron homeostasis in mouse ferroxidase mutants

“…We found dramatically increased cardiac iron comparable to the nutritional iron overloaded mice and suggests that Cp plays an important role in mobilizing iron from the heart. A recent study found expression of both Hp and Cp in the heart but only Cp was responsive to iron levels (Qian et al 2007). As has been previously noted, the Cp -/-mouse has elevated spleen and liver iron.…”

The iron regulatory hormone hepcidin reduces ferroportin 1 content and iron release in H9C2 cardiomyocytes

“…Recently, we investigated expression of iron exporters including ferroportin 1 (Fpn1), ceruloplasmin (CP) and hephaestin (Heph) and provided evidence for their existence in the heart [8]. We also demonstrated that iron has a significant effect on expression of Fpn1 and CP.…”

“…For this reason, the iron levels in tissues must be tightly regulated. The increased iron and iron-mediated injury have been proposed to play an important role in the development of a number of heart disorders, including heart ischemia-reperfusion injury, iron-overload cardiomyopathy, acute myocardial infarction and coronary heart diseases [2][3][4][5][6][7][8]. At present, it is unknown how iron increases to a pathological level in the heart under abnormal circumstances.…”

Alterations of systemic and muscle iron metabolism in human subjects treated with low-dose recombinant erythropoietin

“…It has been shown that iron loading increases ferroportin mRNA and protein levels in macrophages 44,45 and other cells, 3,[46][47][48][49] by acting at transcriptional 45,49 and posttranscriptional 47 levels. In addition to iron, ferroportin expression is posttranslationally mediated by hepcidin.…”