FTH1 Human
Description
Product Specs
The light chain ferritin polypeptide is the primary protein responsible for storing iron inside cells in both prokaryotes and eukaryotes. The specific makeup of ferritin subunits affects how quickly iron is absorbed and released in different tissues. A crucial role of ferritin is to store iron in a way that is both soluble and non-toxic. Defects in the gene responsible for producing this light chain ferritin have been linked to various neurodegenerative diseases and a condition called hyperferritinemia-cataract syndrome.
Ferritin ensures that iron is stored in a soluble, non-toxic form that is readily available when needed. It plays a vital role in maintaining iron balance within the body. Iron is taken into the body in its ferrous form and, after being oxidized, is stored as ferric hydroxides.
Adding a carrier protein like HSA or BSA (0.1%) is recommended for extended storage.
Avoid repeated freezing and thawing.
Q&A
What is the molecular structure of human FTH1 protein?
Human FTH1 (Ferritin Heavy Chain 1) is a 21 kDa protein that possesses ferroxidase activity, converting Fe²⁺ into Fe³⁺. FTH1 can self-assemble with Ferritin Light Chain (FTL) to form a spherical cage with a diameter of approximately 12 nm and an interior cavity of 8 nm . This unique architecture allows ferritin to efficiently sequester iron and reduce Fe²⁺ toxicity . The quaternary structure of ferritin typically contains 24 subunits composed of varying ratios of FTH1 and FTL proteins, depending on the tissue type and physiological conditions.
How does FTH1 expression differ between normal and cancerous tissues?
Analysis of TCGA and GTEx databases reveals that FTH1 expression patterns vary significantly across cancer types. Contrary to what might be expected for an iron storage protein, FTH1 is predominantly downregulated in most human cancers (22 of 27 cancers analyzed, or 81.5%) . It is upregulated in only four cancer types (14.8%): cholangiocarcinoma (CHOL), head and neck squamous cell carcinoma (HNSC), kidney renal clear cell carcinoma (KIRC), and kidney renal papillary cell carcinoma (KIRP) . Only one cancer type (3.7%), uterine corpus endometrial carcinoma (UCEC), showed no significant change in FTH1 expression . This differential expression pattern suggests tissue-specific roles of FTH1 in cancer development.
What is the relationship between FTH1 and tumor prognosis?
FTH1 expression levels correlate with patient prognosis in several cancer types. High FTH1 expression is associated with poor prognosis in 11 cancer types, including head and neck squamous cell carcinoma (HNSC) . Among these 11 cancers with poor prognosis correlation, FTH1 is significantly downregulated in nine cancer types and upregulated in two (KIRP and HNSC) compared to normal tissues . In liver hepatocellular carcinoma, HNSC, lower grade glioma (LGG), and kidney renal papillary cell carcinoma, FTH1 levels are significantly associated with patient survival outcomes . These findings suggest that FTH1 functions as a bifunctional molecule in cancer progression, potentially enhancing or suppressing tumor growth depending on the cancer type.
How does FTH1 interact with FTL in ferritin complex formation?
FTH1 possesses ferroxidase activity that converts Fe²⁺ into Fe³⁺, while its combination with FTL efficiently reduces Fe²⁺ toxicity . The interaction between these two subunits creates a functional ferritin complex capable of storing up to 4500 iron atoms. In most human cancers analyzed, FTL is upregulated (in 21 of 27 cancers, 77.8%), whereas FTH1 is predominantly downregulated . This inverse relationship suggests that the FTH1/FTL ratio, rather than absolute expression of either subunit alone, may be critical in determining ferritin functionality in different tissue types and pathological conditions.
What is the relationship between FTH1 expression and tumor immune microenvironment?
FTH1 expression levels show significant positive correlations with tumor infiltration by various immune cell populations. Analysis using multiple bioinformatics tools (ESTIMATE, MCP-counter, TIMER, and TIMINER) reveals that FTH1 expression positively correlates with immune score in most cancers (22/32, 68.8%) .
FTH1 expression is most strongly associated with:
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Monocytic lineage cells (24/32 cancers, 75.0%)
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Myeloid dendritic cells (17/32 cancers, 53.1%)
Most significantly, FTH1 expression positively correlates with regulatory T cells (Tregs) and tumor-associated macrophages (TAMs) across the majority of cancer types . This suggests that FTH1 may play a crucial role in modulating the immunosuppressive tumor microenvironment, potentially by influencing iron availability to different immune cell populations.
How does FTH1 expression correlate with immune checkpoint molecules?
FTH1 expression shows variable correlation patterns with key immune checkpoint molecules across different cancer types:
| Immune Checkpoint | Positive Correlation with FTH1 | Percentage of Cancers |
|---|---|---|
| PD-1 | 4/32 cancers | 12.5% |
| PD-L1 | 9/32 cancers | 28.1% |
| CTLA4 | 7/32 cancers | 21.9% |
| TIM-3 | 20/32 cancers | 62.5% |
| LAG3 | 2/32 cancers | 6.3% |
| LAIR1 | Significant correlation | Not specified |
The strong positive correlation between FTH1 and TIM-3 (62.5% of cancers) is particularly noteworthy . This suggests that FTH1 may influence T cell exhaustion processes in the tumor microenvironment, potentially through iron-dependent metabolic mechanisms that affect T cell function and persistence.
What mechanisms explain FTH1's impact on regulatory T cells (Tregs)?
FTH1 expression positively correlates with Treg infiltration in most solid tumors . This correlation may be explained by several potential mechanisms:
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Iron-dependent metabolic regulation: Tregs require precise iron homeostasis for proliferation and immunosuppressive functions.
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Oxidative stress modulation: FTH1's ferroxidase activity may protect Tregs from excessive reactive oxygen species.
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Direct signaling: Tumor-secreted FTH1 can activate Tregs to produce interleukin-10, thereby suppressing anti-tumor immune responses .
While T cells generally require iron for metabolic and redox reactions supporting proliferation and effector functions, excessive intracellular iron can induce cell death via oxidative stress . The relationship between FTH1 and Tregs suggests that targeting iron metabolism could be a novel approach to modulate the immunosuppressive tumor microenvironment.
What is the relationship between FTH1 expression and quantitative susceptibility mapping (QSM) in the human brain?
Analysis of brain tissue using quantitative susceptibility mapping (QSM) shows correlations between magnetic susceptibility values and the expression of iron-related genes, including FTH1 . Multiple regression analysis of QSM data versus normalized expression of iron-related genes (including TF, TFRC, SLC40A1, FTH1, FTL, and SLC11A2) in deep grey nuclei regions of the brain demonstrates that FTH1 expression patterns correlate with iron distribution .
This relationship is particularly important in understanding iron homeostasis in the brain, where proper iron regulation is critical for neurological functions including myelin formation. Disruptions in brain iron homeostasis, potentially reflected in altered FTH1 expression, may contribute to various neurological disorders and age-related changes in brain function.
What are the most effective systems for recombinant FTH1 expression and purification?
Recombinant human FTH1 expression presents challenges due to its complex quaternary structure. A novel construct (FTH1-PfTrx-His) has been developed that can be efficiently expressed and purified in Escherichia coli . This construct uses thioredoxin from the archaebacterium Pyrococcus furiosus (PfTrx) as a scaffold protein, which provides superior solubilization capacity and thermal stability .
Key advantages of this expression system include:
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Consistent soluble protein expression
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Compatibility with peptide modifications without compromising expression
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Preserved functionality, including doxorubicin packaging capabilities comparable to natural FTH1
This expression system is particularly valuable for researchers seeking to produce modified versions of FTH1 for applications in drug delivery or molecular imaging, as it allows for peptide insertions without compromising protein expression or assembly.
How can researchers analyze FTH1's role in the tumor microenvironment?
Multiple bioinformatics tools have been established to investigate correlations between FTH1 expression and tumor-infiltrating immune cells:
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ESTIMATE (Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data): Evaluates the immune cell infiltration level based on gene expression data .
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MCP-counter (Microenvironment Cell Population-counter): Quantifies multiple immune and stromal cell populations from transcriptomic data .
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TIMER (Tumor Immune Estimation Resource): Analyzes immune cell infiltrates across diverse cancer types .
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TIMINER (Tumor-Immune Miner): Provides comprehensive analysis of immune cell infiltration patterns .
For experimental validation, researchers should consider:
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Immunohistochemistry to assess FTH1 protein levels and colocalization with immune cell markers
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Flow cytometry to quantify immune cell populations in relation to FTH1 expression
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In vitro co-culture systems to examine direct effects of FTH1 on immune cell function
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Iron chelation experiments to determine whether FTH1's effects are iron-dependent
What approaches can be used to study the clinical significance of FTH1 expression in cancer patients?
To assess the clinical relevance of FTH1 expression, researchers should employ:
How can researchers leverage FTH1's nanocage properties for drug delivery applications?
FTH1's ability to self-assemble into a spherical cage with an interior cavity makes it an excellent candidate for drug delivery applications. Researchers can exploit this natural architecture through several approaches:
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Drug Encapsulation:
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Surface Modification:
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Peptide insertions can be introduced without compromising expression or assembly
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Targeting moieties can direct FTH1 nanocages to specific tissues or cell types
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Release Mechanism Design:
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pH-responsive release for tumor-specific drug delivery
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Redox-sensitive linkers for controlled release in specific cellular compartments
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Imaging Applications:
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Integration of contrast agents for multimodal imaging
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Monitoring of drug delivery and biodistribution
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The dual functionality of FTH1 as both a biological molecule involved in iron homeostasis and a structural scaffold for drug delivery makes it a uniquely versatile platform for translational research applications.
How can multi-omics approaches enhance our understanding of FTH1 function?
Understanding FTH1's complex roles in health and disease requires integration of multiple data types:
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Transcriptomics:
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Analysis of FTH1 expression across tissues and disease states
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Correlation with iron metabolism and immune-related gene signatures
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Proteomics:
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Evaluation of FTH1/FTL ratios in different cellular contexts
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Post-translational modifications affecting ferritin assembly and function
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Metabolomics:
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Assessment of iron-related metabolites in relation to FTH1 expression
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Investigation of metabolic reprogramming in cells with altered FTH1 levels
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Imaging:
Future research should focus on integrating these diverse data types to develop comprehensive models of FTH1 function in specific biological contexts.
What are the emerging therapeutic strategies targeting FTH1 in disease?
Based on current research, several therapeutic approaches targeting FTH1 show promise:
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Immunomodulation:
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Disrupting FTH1-mediated Treg activation to enhance anti-tumor immunity
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Targeting the relationship between FTH1 and immune checkpoint molecules
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Iron Chelation Therapy:
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Modulating FTH1 expression through iron availability
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Combining iron chelators with immunotherapy for enhanced efficacy
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Nanotechnology Applications:
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Gene Therapy:
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Modulating FTH1/FTL ratios in specific tissues
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Correcting aberrant FTH1 expression in diseases with iron dysregulation
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As research in this field advances, a deeper understanding of FTH1's multifaceted roles will likely reveal additional therapeutic opportunities across various disease contexts.
Product Science Overview
Ferritin is a crucial iron-storage protein found in all living organisms, playing a vital role in maintaining iron homeostasis. The human recombinant ferritin heavy chain (FTH1) is a synthetic version of the naturally occurring heavy chain of ferritin, produced through recombinant DNA technology. This article delves into the structure, function, and significance of the ferritin heavy chain, particularly the human recombinant variant.
Ferritin is composed of 24 subunits, forming a hollow spherical shell that can store up to 4500 iron atoms in a non-toxic and soluble form . These subunits are of two types: heavy (H) and light (L) chains. The heavy chain, encoded by the FTH1 gene located on chromosome 11, is responsible for the ferroxidase activity of ferritin, which catalyzes the oxidation of Fe(II) to Fe(III) .
The primary function of ferritin is to store iron in a soluble, non-toxic form and release it in a controlled manner. The heavy chain of ferritin plays a critical role in this process by oxidizing Fe(II) to Fe(III), which is then stored as ferric hydroxides inside the protein shell . This oxidation process is essential for preventing the formation of free radicals, which can cause cellular damage.
Recombinant ferritin heavy chain is produced using Escherichia coli as an expression system . This recombinant protein retains the functional properties of the natural ferritin heavy chain, making it suitable for various research and clinical applications. It is often used in studies related to iron metabolism, neurodegenerative diseases, and as a control in biochemical assays .
Mutations in the FTH1 gene can lead to disorders such as Hemochromatosis type 5, characterized by excessive iron accumulation in the body . Understanding the structure and function of the ferritin heavy chain is crucial for developing therapeutic strategies for such iron-related disorders. Additionally, defects in ferritin proteins have been associated with several neurodegenerative diseases, highlighting the importance of ferritin in maintaining neuronal health .
