Accumulation of protoporphyrin IX from delta-aminolevulinic acid in bovine skin fibroblasts with hereditary erythropoietic protoporphyria. A gene-dosage effect.
Open accessAbstract
Bovine skin fibroblasts accumulated protoporphyrin IX when incubated in culture with the porphyrin-heme precursor, delta-aminolevulinic acid (ALA). Fibroblasts from cattle homozygous for erythropoietic protoporphyria (EPP) and with the clinical symptoms of the disease accumulated approximately sixfold greater amounts of protoporphyrin IX than cells from normal control animals. Cells from obligatory heterozygous animals, which are clinically normal, accumulated an intermediate level of protoporphyrin IX. When these cells were incubated with ALA and CaMg EDTA, all types of cells accumulated approximately the same amount of protoporphyrin IX (approximately 500 nmol/mg protein), suggesting that ferrochelatase activity was equally low after inhibition by treatment with CaMg EDTA in all cells. Thus the ratio of protoporphyrin IX accumulation from ALA in cultures treated with CaMg EDTA compared with controls treated with ALA alone was greatest in normal cells, least in EPP cells, and intermediate in the heterozygote cells. These findings suggest that the amount of protoporphyrin IX accumulation from ALA reflects the extent of deficiency of ferrochelatase and is proportional to the dosage of abnormal EPP gene in cultured fibroblasts. Similarly, stimulation of porphyrin accumulation by CaMg EDTA reflects diminished ferrochelatase activity in these cells. Thus, the results of this study demonstrate the usefulness of estimating protoporphyrin IX formation from ALA for the detection of an EPP gene defect in cultured bovine skin fibroblasts.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
ALA-induced PpIX was much higher in lymphocytes from erythropoietic protoporphyria patients carrying the loss-of-function FECH mutation than in normal human lymphocytes and could be further enhanced by an iron chelator.
“In this early study, ALA-induced PpIX was much higher in lymphocytes from erythropoietic protoporphyria patients (carrying the loss-of-function mutation of the FECH gene) than in normal human lymphocytes and could be further enhanced by an iron chelator, suggesting the importance of FECH and ferrous iron in regulating PpIX level.”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [15]
The Results (p. 1096) report that CaMg EDTA increased PpIX in mitogen-stimulated human lymphocytes, including those from EPP patients; the Discussion (pp. 1099–1100) links ALA-induced PpIX accumulation to ferrochelatase deficiency. But this paper’s own comparative experiments used bovine skin fibroblasts, and its account of the earlier human lymphocyte study does not establish that patients’ ALA-induced PpIX was “much higher” than controls’. (LLM, conf=0.82)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 315,771 · see citing works
Granick, S., Sinclair, P. R., Sassa, S., & Grieninger, G. (1975) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)40633-9 · Cited by 306 · see citing works
Self-citationPorra, R. J., & JONES, O. (1963) · Biochemical Journal · doi:10.1042/bj0870181 · Cited by 290 · see citing works
Bonkowsky, H. L., Bloomer, J. R., Ebert, P. S., & Mj, M. (1975) · Journal of Clinical Investigation · doi:10.1172/jci108189 · Cited by 239 · see citing works
Sassa, S., & Kappas, A. (1977) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)40571-0 · Cited by 160 · see citing works
Self-citationSassa, S., Solish, G. I., Levere, R. D., & Kappas, A. (1975) · The Journal of Experimental Medicine · doi:10.1084/jem.142.3.722 · Cited by 82 · see citing works
Self-citationSassa, S., Zalar, G. L., & Kappas, A. (1978) · Journal of Clinical Investigation · doi:10.1172/jci108961 · Cited by 77 · see citing works
Self-citationBovine Protoporphyria: The First Nonhuman Model of This Hereditary Photosensitizing Disease
Ruth, G. R., Schwartz, S., & Stephenson, B. D. (1977) · Science · doi:10.1126/science.905823 · Cited by 69 · see citing works
Self-citationBloomer, J. R., Brenner, D. A., & Mahoney, M. (1977) · Journal of Clinical Investigation · doi:10.1172/jci108895 · Cited by 52 · see citing works
Bloomer, J. R. (1980) · Journal of Clinical Investigation · doi:10.1172/jci109675 · Cited by 38 · see citing works
(1979) · PubMed · Cited by 6 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Yager, J. A., & Scott, D. W. (1993) · Elsevier eBooks · doi:10.1016/b978-0-08-057133-1.50013-8 · Cited by 257 · see citing works
ALA and its clinical impact, from bench to bedside
Krammer, B. E., & Plaetzer, K. (2007) · Photochemical & Photobiological Sciences · doi:10.1039/b712847a · Cited by 252 · see citing works
Beri, R., & Chandra, R. (1993) · Drug Metabolism Reviews · doi:10.3109/03602539308993973 · Cited by 68 · see citing works
Metal ion-mediated regulation of heme oxygenase induction in cultured avian liver cells.
Sardana, M. K., Sassa, S., & Kappas, A. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)34597-6 · Cited by 48 · see citing works
Self-citationEFFECT OF UVA AND BLUE LIGHT ON PORPHYRIN BIOSYNTHESIS IN EPIDERMAL CELLS*
Sassa, D. H. S., & Hw, L. (1993) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.1993.tb09218.x · Cited by 42 · see citing works
Iwasa, F., Sassa, S., & Kappas, A. (1989) · Biochemical Journal · doi:10.1042/bj2620807 · Cited by 39 · see citing works
Self-citation5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy
Howley, R., Chandratre, S., & Chen, B. (2023) · Bioengineering · doi:10.3390/bioengineering10040496 · Cited by 33 · see citing works
Enhancement of photodynamic therapy in gastric cancer cells by removal of iron.
Tan, W. C., Krasner, N., O'Toole, P., & Lombard, M. (1997) · Gut · doi:10.1136/gut.41.1.14 · Cited by 31 · see citing works
Sassa, S., Zalar, G. L., Poh‐Fitzpatrick, M. B., Anderson, K. E., & Kappas, A. (1982) · Journal of Clinical Investigation · doi:10.1172/jci110520 · Cited by 29 · see citing works
Self-citationPorphyrias: Animal models and prospects for cellular and gene therapy
de Verneuil, H., Ged, C., Boulechfar, S., & Moreau‐Gaudry, F. (1995) · Journal of Bioenergetics and Biomembranes · doi:10.1007/bf02110039 · Cited by 27 · see citing works
THE EFFECT OF ALA AND RADIATION ON PORPHYRIN/HEME BIOSYNTHESIS IN ENDOTHELIAL CELLS
He, D., Behar, S., Nomura, N., Sassa, S., & Lim, H. W. (1995) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.1995.tb09884.x · Cited by 24 · see citing works
Self-citationPalasuberniam, P., Kraus, D., Mansi, M., Braun, A., Howley, R., Myers, K. A., & Chen, B. (2019) · Photochemistry and Photobiology · doi:10.1111/php.13091 · Cited by 23 · see citing works
Ishino, T., Hashimoto, M., Amagasa, M., SAITO, N., Dochi, O., KIRISAWA, R., & Kitamura, H. (2018) · Biomedical Research · doi:10.2220/biomedres.39.95 · Cited by 21 · see citing works
Dutta, S., Kolli, B. K., Tang, A., Sassa, S., & Chang, K. P. (2008) · Eukaryotic Cell · doi:10.1128/ec.00365-07 · Cited by 20 · see citing works
Self-citationJohansson, A., Möller, C., & Harper, P. (2003) · Molecular and Cellular Biochemistry · doi:10.1023/a:1024946216776 · Cited by 18 · see citing works
Ferrochelatase Activity in Human Lymphocytes: Effect of Storage on Haem Formation
Tovey, J. A., & Elder, G. H. (1990) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1177/000456329002700118 · Cited by 1 · see citing works
Sassa, S., Zalar, G. L., Poh‐Fitzpatrick, M. B., Anderson, K. E., & Kappas, A. (1982) · Cited by 1 · see citing works
Self-citationPhotodynamische Diagnostik in der Dermatologie
Fritsch, C., Neuse, W. H. G., Ruzicka, T., & Goerz, G. (1997) · Springer eBooks · doi:10.1007/978-3-642-60425-6_19 · Cited by 1 · see citing works
(2007) · Elsevier eBooks · doi:10.1016/b978-070202823-6.50075-0
- Authors
- Sassa, S., Schwartz, S., & Ruth, G.
- ORCID
- Schwartz, S
- Venue
- The Journal of experimental medicine
- Publisher
- Rockefeller University Press
- Published
- 1981-05-01
- Volume
- 153
- Issue
- 5
- Pages
- 1094-1101
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2186152
- OpenAlex
- W2134286645
- Cited by
- 19
- References
- 11
- Citations by year
- 2023: 1 · 2019: 1 · 2018: 1
- FWCI
- 0.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal Health and Biochemistry
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Keywords
- protoporphyrin IX accumulation, 5-aminolevulinic acid, ferrochelatase deficiency, gene dosage effect, heterozygote detection, genetic diagnosis
- MeSH terms
- Aminolevulinic Acid, Animals, Cattle, Edetic Acid, Erythropoiesis, Fibroblasts, Iron, Levulinic Acids, Porphyrias, Porphyrins, Protoporphyrins, Skin, Protoporphyria, Erythropoietic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
