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Table 1 Expression, regulation and action of brain hepcidin

From: Hepcidin, an emerging and important player in brain iron homeostasis

Methods

Study conditions

Main results

References

Expression measured with RT-PCR from human tissues

Physiological conditions

mRNA of hepcidin present in brain tissue

Krause et al. [31]

Expression measured with RT-PCR from human tissues

Physiological conditions

mRNA of hepcidin present in spinal cord

Pigeon et al. [1]

Expression measured with RT-PCR, in situ hybridization, immunohistochemistry in murine brain

Physiological conditions

Hepcidin expression detected with RT-PCR and in situ hybridization

Immunohistochemistry showed a wide distribution of the protein across the brain tissue compared to narrow distribution of mRNA of hepcidin measured by in situ hybridization

Zechel et al. [32]

Expression measured with RT-PCR and in situ hybridization, while protein levels were measured with western blotting and immunohistochemistry (rat brain samples)

Physiological conditions

Hepcidin expression was low with highest signal detected in choroidal plexus and to a lesser extent in blood vessels

Protein levels were abundant, especially in blood vessels, choroidal plexus and cortical astrocytes in close proximity to blood vessels

Raha-Chowdhury et al. [33]

Protein levels measured with western blotting and immunohistochemistry (mouse brain samples)

Physiological conditions

Abundant protein levels of hepcidin across the brain tissue

Raha et al. [35]

Expression measured with RT-PCR, while protein levels were measured with western blotting (mouse brain and cell cultures)

Physiological and stimulated conditions

Hepcidin expression was abundant but still in low levels

Hepcidin induced FPN downregulation in mouse brain

Hepcidin decreases iron-release in cultured neurons due to FPN downregulation

Wang et al. [34]

Expression measured with RT-PCR (human brain samples)

Physiological conditions

HJV mRNA was not observed

Hepcidin, neogenin, TFR2, HFE mRNA was present

Hänninen et al. [69]

Expression measured with RT-PCR, while protein levels were measured with western blotting (mouse brain)

Different stimulated conditions

TFR2 loss does not affect brain hepcidin protein levels

Pellegrino et al. [73]

Expression measured with RT-PCR, while protein levels were measured with western blotting and immunohistochemistry (rat cultured cells)

Inflammation

Microglia react to LPS by producing IL-6

Astrocytes produce hepcidin in response to IL-6 secreted by microglia

Hepcidin increases iron-load in neurons

Inflammation has hepcidin-independent actions in reducing iron-export and enhancing iron-import in neurons

You et al. [54]

Expression measured with RT-PCR, while protein levels were measured by western blotting and immunohistochemistry (rat cultured cells)

Inflammation and iron-stimulation

TNF-α, IL-6 and LPS increase cellular iron content in neurons

TNF-α, IL-6 and LPS do not affect cellular iron content in astrocytes

TNF-α, IL-6 and LPS increase cellular iron content in microglia

TNF-α, IL-6 and LPS cause DMT1↑ and FPN↓ (protein levels) in neurons

TNF-α, IL-6 and LPS cause DMT1↑ (protein levels) in astrocytes

TNF-α, IL-6 and LPS cause DMT1↑ (protein levels) in microglia

TNF-α, IL-6 and LPS cause DMT1↑ (mRNA) in neurons

TNF-α, IL-6 and LPS cause DMT1↑ (mRNA), while LPS causes FPN↓ in astrocytes

TNF-α, IL-6 and LPS cause DMT1↑ (mRNA), while TNF-α and LPS cause FPN↓ (mRNA) in microglia

TNF-α, IL-6, LPS and FeNTA cause hepcidin↑(mRNA) in astrocytes and microglia but not in neurons

Urrutia et al. [56]

Protein levels measured with western blotting and ELISA in rat cultured cells

Inflammation

LPS increases hepcidin expression in rat brain

LPS increases IL-6 production from microglia

IL-6 from microglia induces hepcidin production in neurons (via STAT3 pathway)

No observed hepcidin↑ in neurons without co-cultured microglia due to LPS stimulation

Qian et al. [55]

Expression measured with RT-PCR, while protein levels were measured with western blotting and immunohistochemistry (rat brain and cultured cells)

Iron-overload

Hepcidin↑ in rat brain and cultured cells

Hepcidin mRNA↑ in cultured neurons in response to iron-overload

Sun et al. [64]

Expression measured with RT-PCR, while protein levels were measured with western blotting and ELISA in rat brain and cultured cells

Iron-overload

Hepcidin reduces iron-load in rat brains

Hepcidin induces TFR1↓, DMT1↓ and FPN↓ in BMEC

Hepcidin induces TFR1↓, DMT1↓ and FPN↓ in neurons

Du et al. [59]

Expression measured with RT-PCR, while protein levels were measured with western blotting and ELISA in rat brain and cultured cells

Physiological conditions

Hepcidin induces TFR1↓, DMT1↓ and FPN↓ in astrocytes

TFR1↓ is realized through AMPK pathway

Du et al. [58]

Expression measured by RT-PCR, while levels of chemicals were measured with ELISA

Inflammation induced by Aβ aggregates

Hepcidin pre-treatment reduces expression and secretion of IL-6 and TNF-α in astrocytes and microglia

Urrutia et al. [65]

  1. Aβ amyloid beta, AMPK AMP-activated protein kinase, BMEC brain microvascular endothelial cells, DMT1 divalent metal transporter 1, ELISA enzyme-linked immunosorbent assay, FeNTA ferric nitrilotriacetate, FPN ferroportin, HFE hemochromatosis protein, HJV hemojuvelin, IL-6 interleukin 6, LPS lipopolysaccharide, RT-PCR reverse transcription polymerase chain reaction, STAT3 signal transducer and activator of transcription 3, TFR transferrin receptor, TNF-α tumor necrosis factor-alpha