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Translational control of inducible nitric oxide synthase expression by arginine can explain the arginine paradox
Lee J, Ryu H, Ferrante RJ, Morris SM, Ratan RR.. Proceedings of the National Academy of Sciences of the United States of America, 2003-03-24
Topic: Brain proteins, microglia and lab models
L-Arginine is the only endogenous nitrogen-containing substrate of NO synthase (NOS), and it thus governs the production of NO during nervous system development as well as in disease states such as stroke, multiple sclerosis, Parkinson's disease, and HIV dementia. The "arginine paradox" refers to the dependence of cellular NO production on exogenous L-arginine concentration despite the theoretical saturation of NOS enzymes with intracellular L-arginine. Herein, we report that decreased availability of L-arginine blocked induction of NO production in cytokine-stimulated astrocytes, owing to inhibition of inducible NOS (iNOS) protein expression.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Lee, J., Ryu, H., Ferrante, R. J., Morris, S. M., & Ratan, R. R. (2003). Translational control of inducible nitric oxide synthase expression by arginine can explain the arginine paradox. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.0735876100
Vancouver
Lee J, Ryu H, Ferrante RJ, Morris SM, Ratan RR. Translational control of inducible nitric oxide synthase expression by arginine can explain the arginine paradox. Proceedings of the National Academy of Sciences of the United States of America. 2003. doi:10.1073/pnas.0735876100. PMID: 12655043.
BibTeX
@article{lee2003-12655043,
author = {Lee, J. and Ryu, H. and Ferrante, R. J. and Morris, S. M. and Ratan, R. R.},
title = {{Translational control of inducible nitric oxide synthase expression by arginine can explain the arginine paradox}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2003},
doi = {10.1073/pnas.0735876100},
pmid = {12655043},
url = {https://doi.org/10.1073/pnas.0735876100}
}
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Key findings
- The "arginine paradox" refers to the dependence of cellular NO production on exogenous L-arginine concentration despite the theoretical saturation of NOS enzymes with intracellular L-arginine.
- Herein, we report that decreased availability of L-arginine blocked induction of NO production in cytokine-stimulated astrocytes, owing to inhibition of inducible NOS (iNOS) protein expression.
- However, activity of the promoter of the iNOS gene, induction of iNOS mRNA, and stability of iNOS protein were not inhibited under these conditions.
- Our results indicate that inhibition of iNOS activity by arginine depletion in stimulated astrocyte cultures occurs via inhibition of translation of iNOS mRNA.
Why it matters
This laboratory study found that limiting L-arginine blocked nitric oxide production in cytokine-stimulated astrocytes by preventing iNOS protein expression. It is cell-level research and does not show a treatment for Alzheimer's disease.
Study details
- Evidence strengthLow
How this study scored 49/100
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 (Proceedings of the National Academy of Sciences of the United States of America) |
| Journal's citation record | 4 / 4 | Proceedings of the National Academy of Sciences: journal h-index 1,167 (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 | 2003 — 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 | 6 / 7 | Cited 359 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 14.4 citations a year over 25 year(s) since 2003 |
| Impact for its field and year | 4 / 6 | Cited 13.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 27 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Rajiv R. Ratan: h-index 77 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 12655043) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 49 / 100 | — |
What each of these 20 components measures, and what this score is not →
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