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Glial HO-1 expression, iron deposition and oxidative stress in neurodegenerative diseases
Schipper HM.. Neurotoxicity research, 1999-09-01
Topic: Brain proteins, microglia and lab models
The mechanisms responsible for the pathological deposition of brain iron in Parkinson's disease, Alzheimer's disease and other human neurodegenerative disorders remain poorly understood. In rat primary astrocyte cultures, we demonstrated that dopamine, cysteamine, H(2)O(2) and menadione rapidly induce heme oxygenase-1 (HO-1) expression (mRNA and protein) followed by sequestration of non-transferrin-derived (55)Fe by the mitochondrial compartment. The effects of dopamine on HO-1 expression were inhibited by ascorbate implicating a free radical mechanism of action. Dopamine-induced mitochondrial iron trapping was abrogated by administration of the heme oxygenase inhibitors, tin mesoporphyrin (SnMP) or dexamethasone (DEX) indicating that HO-1 upregulation is necessary for subsequent mitochondrial iron deposition in these cells. Overexpression of the human HO-1 gene in cultured rat astroglia by transient transfection also stimulated mitochondrial (55)Fe deposition, an effect that was again preventible by SnMP or DEX administration. We hypothesize that free ferrous iron and carbon monoxide generated by HO-1-mediated heme degradation promote mitochondrial membrane injury and the deposition of redox-active iron within this organelle. We have shown that the percentages of GFAP-positive astrocytes that co-express HO-1 in Parkinson-affected substantia nigra and Alzheimer-diseased hippocampus are significantly increased relative to age-matched controls. Stress-induced up-regulation of HO-1 in astroglia may be responsible for the abnormal patterns of brain iron deposition and mitochondrial insufficiency documented in various human neurodegenerative disorders.
Key findings
- In rat primary astrocyte cultures, we demonstrated that dopamine, cysteamine, H(2)O(2) and menadione rapidly induce heme oxygenase-1 (HO-1) expression (mRNA and protein) followed by sequestration of non-transferrin-derived (55)Fe by the mitochondrial compartment.
- We have shown that the percentages of GFAP-positive astrocytes that co-express HO-1 in Parkinson-affected substantia nigra and Alzheimer-diseased hippocampus are significantly increased relative to age-matched controls.
Why it matters
In rat astrocyte cultures, dopamine and other agents triggered HO-1 expression and mitochondrial iron buildup, and HO-1 inhibitors blocked this iron trapping. Astrocytes co-expressing HO-1 were increased in Parkinson's substantia nigra and Alzheimer's hippocampus compared with age-matched controls, suggesting a possible role for HO-1 in iron deposition in these diseases.
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Study details
- Evidence strengthLow
How this study scored 32/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurotoxicity research) |
| Journal's citation record | 1 / 4 | Neurotoxicity Research: journal h-index 103 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 1999 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 72 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.5 citations a year over 29 year(s) since 1999 |
| Impact for its field and year | 1 / 6 | Cited 0.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 4 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Hyman M. Schipper: h-index 58 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Lady Davis Institute for Medical Research: institution h-index 428 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 12835114) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 32 / 100 | — |
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Read the original
May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Schipper, H. M. (1999). Glial HO-1 expression, iron deposition and oxidative stress in neurodegenerative diseases. Neurotoxicity research. https://doi.org/10.1007/bf03033339
Vancouver
Schipper HM. Glial HO-1 expression, iron deposition and oxidative stress in neurodegenerative diseases. Neurotoxicity research. 1999. doi:10.1007/bf03033339. PMID: 12835114.
BibTeX
@article{schipper1999-12835114,
author = {Schipper, H. M.},
title = {{Glial HO-1 expression, iron deposition and oxidative stress in neurodegenerative diseases}},
journal = {Neurotoxicity research},
year = {1999},
doi = {10.1007/bf03033339},
pmid = {12835114},
url = {https://doi.org/10.1007/bf03033339}
}
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