This review provides a synopsis of the published literature over the past two years on the heme-binding protein hemopexin (HPX), with some background information on the biochemistry of the HPX system. One focus is on the mechanisms of heme-driven pathology in the context of heme and iron homeostasis in human health and disease. The heme-binding protein hemopexin is a multi-functional protectant against hemoglobin (Hb)-derived heme toxicity as well as mitigating heme-mediated effects on immune cells, endothelial cells, and stem cells that collectively contribute to driving inflammation, perturbing vascular hemostasis and blood–brain barrier function. Heme toxicity, which may lead to iron toxicity, is recognized increasingly in a wide range of conditions involving hemolysis and immune system activation and, in this review, we highlight some newly identified actions of heme and hemopexin especially in situations where normal processes fail to maintain heme and iron homeostasis. Finally, we present preliminary data showing that the cytokine IL-6 cross talks with activation of the c-Jun N-terminal kinase pathway in response to heme-hemopexin in models of hepatocytes. This indicates another level of complexity in the cell responses to elevated heme via the HPX system when the immune system is activated and/or in the presence of inflammation.

Obesity has been implicated in the induction of oxidative stress, which is thought to contribute to the pathogenesis of various cardiovascular diseases, including cardiac hypertrophy. However, the redox status during the early stages of cardiac hypertrophy remains inadequately characterized. In this study, we administered a high-fat diet (HFD) to C57BL/6N mice for 12 weeks. We investigated the expression of biomarkers associated with hypertrophy and oxidative stress, including lipid peroxidation, protein carbonylation, and the redox couples NADH/NAD⁺, NADPH/NADP⁺, and GSH/GSSG. Additionally, we assessed the expression levels and enzymatic activities of catalase, glutathione peroxidase, glutathione reductase, and superoxide dismutase. Following 12 weeks on a HFD, mice exhibited obesity and a 10% increase in the heart weight/tibia length ratio, together with an upregulation in the mRNA levels of β-myosin heavy chain, brain natriuretic peptide, and regulator of calcineurin 1, isoform 4. There was also a significant increase in NOX4 content in the heart of these animals; however, we observed no rise in protein carbonylation and a decrease in lipid peroxidation products. As for the redox couples, the GSH/GSSG ratio nearly doubled, while the NADH/NAD⁺ and NADPH/NADP⁺ ratios remained stable. All antioxidant enzyme mRNAs examined showed increased expression; however, only glutathione reductase showed higher activity. Our findings suggest that reductive stress is predominant within the cardiac environment of these animals.

This review provides a synopsis of the published literature for the past two years on the heme-binding protein hemopexin (HPX), with some background information on the biochemistry of the HPX system. One focus is on the mechanisms of heme-driven pathology in the context of heme and iron homeostasis in human health and disease. HPX is a multi-functional protectant against hemoglobin (Hb)-derived heme toxicity as well as mitigating heme-mediated effects on immune cells, endothelial cells and stem cells that collectively contribute to driving inflammation, perturb vascular hemostasis and blood-brain barrier function. Heme toxicity is recognized increasingly in a wide range of conditions involving hemolysis and immune system activation and, in this review, we highlight some newly identified actions of heme and hemopexin especially in situations where normal processes fail to maintain heme and iron homeostasis. Finally, we present preliminary data showing that the cytokine IL-6 cross-talks with activation of the Jun N-terminal kinase (JNK) pathway in response to heme-hemopexin in models of hepatocytes. This indicates another level of complexity in the cell responses to elevated heme.