The DOI matches its Crossref record; 199 of the 200 references it cites were found in a registry or an index.
Coupling Heme and Iron Metabolism via Ferritin H Chain
Open accessAbstract
SIGNIFICANCE: Inflammation and immunity can be associated with varying degrees of heme release from hemoproteins, eventually leading to cellular and tissue iron (Fe) overload, oxidative stress, and tissue damage. Presumably, these deleterious effects contribute to the pathogenesis of systemic infections. RECENT ADVANCES: Heme release from hemoglobin sensitizes parenchyma cells to undergo programmed cell death in response to proinflammatory cytokines, such as tumor necrosis factor. This cytotoxic effect is driven by a mechanism involving intracellular accumulation of free radicals, which sustain the activation of the c-Jun N-terminal kinase (JNK) signaling transduction pathway. While heme catabolism by heme oxygenase-1 (HO-1) prevents programmed cell death, this cytoprotective effect requires the co-expression of ferritin H (heart/heavy) chain (FTH), which controls the pro-oxidant effect of labile Fe released from the protoporphyrin IX ring of heme. This antioxidant effect of FTH restrains JNK activation, whereas JNK activation inhibits FTH expression, a cross talk that controls metabolic adaptation to cellular Fe overload associated with systemic infections. CRITICAL ISSUES AND FUTURE DIRECTIONS: Identification and characterization of the mechanisms via which FTH provides metabolic adaptation to tissue Fe overload should provide valuable information to our current understanding of the pathogenesis of systemic infections as well as other immune-mediated inflammatory diseases.
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In the citing paper
“Cytokine-driven NF-jB activation induces FTH transcription, supporting further retention of Fe in Mø [54,55] (Fig 2).”
From The Iron age of host–microbe interactions (2015) · cites this paper as [54]
In the citing paper
“For example, heme catabolism by and subsequent intracellular Fe storage by ferritin [54,107] confers host protection against the blood stage of Plasmodium infection while increasing susceptibility to the intracellular bacteria Salmonella [108].”
From The Iron age of host–microbe interactions (2015) · cites this paper as [54]
In the citing paper
“When coupled to other mechanisms regulating Fe homeostasis, HO-1 avoids tissue Fe overload and tissue damage while sustaining Fe supply to erythropoiesis to maintain Fe homeostasis during infection [38,54,219,220] (Fig 4).”
From The Iron age of host–microbe interactions (2015) · cites this paper as [54]
In the citing paper
“In the context of systemic infections, the protective effects exerted by HO-1 are assisted by FTH [54,107] (Fig 4).”
From The Iron age of host–microbe interactions (2015) · cites this paper as [54]
In the citing paper
“The most abundant pool of Fe in mammals are the prosthetic heme groups of hemoglobin in red blood cells (RBC), followed by the heme groups of myoglobin in muscle cells and those of cytochromes and other ubiquitously expressed hemoproteins in all cells[38,54].”
From The Iron age of host–microbe interactions (2015) · cites this paper as [54]
In the citing paper
“Ferritins are evolutionary conserved multimeric protein complexes composed of adjustable ratios of heart/heavy chain (FTH) and liver/light chain (FTL) proteins, encoded by two distinct genes (45, 46).”
From Innate Nutritional Immunity (2018) · cites this paper as [45]
In the citing paper
“These pathologic trade-offs are countered by tissue damage control mechanisms that limit the deleterious effects of cellular Fe overload (5, 44), via different mechanisms that involve Fe storage and neutralization by ferritin (44, 45).”
From Innate Nutritional Immunity (2018) · cites this paper as [45]
In the citing paper
“The ferroxidase activity of FTH is critical for the conversion of Fe2+ into Fe3+, allowing the storage of 4500 Fe3+ atoms per ferritin complex (45, 46).”
From Innate Nutritional Immunity (2018) · cites this paper as [45]
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Metadata
- Authors
- Gozzelino, R., & Soares, M. P.
- Affiliations
- Instituto Gulbenkian de Ciência (PT)
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2014-04
- Volume
- 20
- Issue
- 11
- Pages
- 1754-1769
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- PMC
- PMC3961798
- OpenAlex
- W2043791600
- Cited by
- 151
- References
- 200
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 14 · 2023: 11 · 2022: 9 · 2021: 10 · 2020: 12 · 2019: 16 · 2018: 11 · 2017: 14 · 2016: 10 · 2015: 13 · 2014: 9
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Antioxidants and Redox Signaling (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Keywords
- heme metabolism, iron metabolism, heme release, hemoglobin, heme oxygenase-1, c-Jun N-terminal kinase, programmed cell death, TNF-α, oxidative stress, iron overload, systemic infection, inflammation, protoporphyrin IX, antioxidant defense, immune-mediated inflammatory diseases
- MeSH terms
- Animals, Apoferritins, Heme, Homeostasis, Humans, Immunity, Innate, Iron, Heme Oxygenase-1
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