Cited by 129Heme Oxygenase-1 and Carbon MonoxideMultiple Sclerosis Research StudiesIron Metabolism and Disorders

Proinflammatory cytokines promote glial heme oxygenase-1 expression and mitochondrial iron deposition: implications for multiple sclerosis

Mehindate, K., Sahlas, D. J., Frankel, D., Mawal, Y., Liberman, A., Corcos, J., Dion, S., Schipper, H. M.·2001·Journal of Neurochemistry

Abstract

Proinflammatory cytokines, pathological iron deposition, and oxidative stress have been implicated in the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). HO-1 mRNA levels and mitochondrial uptake of [(55)Fe]Cl(3)-derived iron were measured in rat astroglial cultures exposed to interleukin-1beta (IL-1beta) or tumor necrosis factor-alpha (TNF-alpha) alone or in combination with the heme oxygenase-1 (HO-1) inhibitors, tin mesoporphyrin (SnMP) or dexamthasone (DEX), or interferon beta1b (INF-beta). HO-1 expression in astrocytes was evaluated by immunohistochemical staining of spinal cord tissue derived from MS and control subjects. IL-1beta or TNF-alpha promoted sequestration of non-transferrin-derived (55)Fe by astroglial mitochondria. HO-1 inhibitors, mitochondrial permeability transition pore (MTP) blockers and antioxidants significantly attenuated cytokine-related mitochondrial iron sequestration in these cells. IFN-beta decreased HO-1 expression and mitochondrial iron sequestration in IL-1beta- and TNF-alpha-challenged astroglia. The percentage of astrocytes coexpressing HO-1 in affected spinal cord from MS patients (57.3% +/- 12.8%) was significantly greater (p < 0.05) than in normal spinal cord derived from controls subjects (15.4% +/- 8.4%). HO-1 is over-expressed in MS spinal cord astroglia and may promote mitochondrial iron deposition in MS plaques. In MS, IFN-beta may attenuate glial HO-1 gene induction and aberrant mitochondrial iron deposition accruing from exposure to proinflammatory cytokines.

Integrity signals

Registry

Crossref · 10.1046/j.1471-4159.2001.00354.x

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  • Incubation with interferon β reverted cytokine-dependent induction of HO-1 and subsequent incorporation of iron into mitochondria.

    “Incubation with interferon β reverted the cytokine-dependent induction of HO-1 and the subsequent incorporation of iron into mitochondria.162”
  • Increased HO-1 expression promoted sequestration of non-transferrin iron into the astroglial mitochondrial compartment, as assayed by 55Fe incorporation.

    “Increased HO-1 expression promoted the sequestration of non-transferrin iron into the astroglial mitochondrial compartment, as assayed by 55Fe incorporation.”
  • In-vitro studies of rat astroglial cultures showed proinflammatory cytokines (interleukin 1β and tumour necrosis factor α) increased HO-1 expression after 6 days of incubation.

    “In-vitro studies of rat astroglial cultures showed that proinflammatory cytokines (ie, interleukin 1β and tumour necrosis factor α) increased HO-1 expression after 6 days of incubation.”

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Authors
Mehindate, K., Sahlas, D. J., Frankel, D., Mawal, Y., Liberman, A., Corcos, J., Dion, S., & Schipper, H. M.
Affiliations
  • Jewish General Hospital (CA)
  • McGill University (CA)
Corresponding author
Schipper, H. M.
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2001-06
Volume
77
Issue
5
Pages
1386-1395
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
OpenAlex
W1902487112
Cited by
129
References
54
Citations by year
2025: 1 · 2024: 4 · 2023: 5 · 2022: 1 · 2021: 1 · 2020: 4 · 2019: 2 · 2018: 3 · 2017: 7 · 2016: 2 · 2015: 5 · 2014: 7 · 2013: 3 · 2012: 3
FWCI
2.79
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Fonds de Recherche du Québec - Santé
  • Medical Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Keywords
heme oxygenase-1, multiple sclerosis, inflammatory cytokines, IL-1β, TNF-α, astrocytes, iron sequestration, interferon-beta, experimental autoimmune encephalomyelitis, oxidative stress, mitochondrial permeability transition pore, tin mesoporphyrin, dexamethasone
MeSH terms
Animals, Cells, Cultured, Chlorides, Encephalomyelitis, Autoimmune, Experimental, Female, Ferric Compounds, Heme Oxygenase (Decyclizing), Humans, Immunohistochemistry, Interleukin-1, Iron, Iron Radioisotopes, Mitochondria, Multiple Sclerosis, Neuroglia, RNA, Messenger, Spinal Cord, Subcellular Fractions, Transferrin, Tumor Necrosis Factor-alpha, Blotting, Northern, Cytokines, Rats, Sprague-Dawley, Rats

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