Patients with erythropoietic protoporphyria have reduced erythrocyte protoporphyrin IX from early in pregnancy

2017 ◽  
Vol 177 (3) ◽  
Author(s):  
I.M. Heerfordt ◽  
H.C. Wulf
Keyword(s):  
Protoporphyrin Ix ◽  
Erythropoietic Protoporphyria ◽  
Erythrocyte Protoporphyrin ◽  
In Pregnancy

scholarly journals Uptake of protoporphyrin IX by isolated rat liver mitochondria

1980 ◽  
Vol 188 (2) ◽  
pp. 329-335 ◽  
Author(s):  
M E Koller ◽  
I Romslo
Keyword(s):  
Rat Liver ◽  
Mitochondrial Membrane ◽  
Protoporphyrin Ix ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Inner Mitochondrial Membrane ◽  
Erythropoietic Protoporphyria ◽  
Inner Membrane ◽  
Isolated Rat Liver ◽  
Isolated Rat

Rat liver mitochondria accumulate protoporphyrin IX from the suspending medium into the inner membrane in parallel with the magnitude of the transmembrane K+ gradient (K+in/K+out). Only protoporphyrin IX taken up in parallel with the transmembrane K+ gradient is available for haem synthesis. Coproporphyrins (isomers I and III) are not taken up by the mitochondria. The results support the suggestion by Elder & Evans [(1978) Biochem. J. 172, 345-347] that the prophyrin to be taken up by the inner mitochondrial membrane belongs to the protoporphyrin(ogen) IX series. Protoporphyrin IX at concentrations above 15 nmol/mg of protein has detrimental effects on the structural and functional integrity of the mitochondria. The relevance of these effects to the hepatic lesion in erythropoietic protoporphyria is discussed.

Erythrocyte Protoporphyrin IX as a Diagnostic and Therapy Evaluating Tool in Lead Poisoning

1981 ◽  
Vol 36 (1) ◽  
pp. 40-43 ◽  
Author(s):  
MIGUEL ANGEL ZÚÑIGA-CHARLES ◽  
J. DIEGO GONZÁLEZ-RAMÍREZ ◽  
GILBERTO MOLINA-BALLESTEROS
Keyword(s):  
Lead Poisoning ◽  
Protoporphyrin Ix ◽  
Erythrocyte Protoporphyrin

scholarly journals The essential role of the transporter ABCG2 in the pathophysiology of erythropoietic protoporphyria

2019 ◽  
Vol 5 (9) ◽  
pp. eaaw6127 ◽  
Author(s):  
Pengcheng Wang ◽  
Madhav Sachar ◽  
Jie Lu ◽  
Amina I. Shehu ◽  
Junjie Zhu ◽  
...  
Keyword(s):  
Essential Role ◽  
Protoporphyrin Ix ◽  
Heme Biosynthesis ◽  
Biosynthesis Pathway ◽  
Efflux Transporter ◽  
Inherited Disease ◽  
Loss Of Function ◽  
Erythropoietic Protoporphyria

Erythropoietic protoporphyria (EPP) is an inherited disease caused by loss-of-function mutations of ferrochelatase, an enzyme in the heme biosynthesis pathway that converts protoporphyrin IX (PPIX) into heme. PPIX accumulation in patients with EPP leads to phototoxicity and hepatotoxicity, and there is no cure. Here, we demonstrated that the PPIX efflux transporter ABCG2 (also called BCRP) determines EPP-associated phototoxicity and hepatotoxicity. We found that ABCG2 deficiency decreases PPIX distribution to the skin and therefore prevents EPP-associated phototoxicity. We also found that ABCG2 deficiency protects against EPP-associated hepatotoxicity by modulating PPIX distribution, metabolism, and excretion. In summary, our work has uncovered an essential role of ABCG2 in the pathophysiology of EPP, which suggests the potential for novel strategies in the development of therapy for EPP.

Erythrocyte Protoporphyrin and Iron Uptake in Erythropoietic Protoporphyria

1971 ◽  
Vol 41 (4) ◽  
pp. 363-370 ◽  
Author(s):  
K. G. A. Clark ◽  
D. C. Nicholson
Keyword(s):  
Fluorescence Microscopy ◽  
Iron Uptake ◽  
Cell Column ◽  
Erythropoietic Protoporphyria ◽  
Mutual Dependence ◽  
Erythrocyte Protoporphyrin

1. Erythrocytes from patients with erythropoietic protoporphyria (E.P.P.) were incubated with radioactive iron, washed and centrifuged. Serial layers were removed from the packed cell columns. The radioactivity and protoporphyrin content of each layer was measured. Blood and marrow aspirates were examined by fluorescence microscopy. 2. The youngest erythrocytes were most fluorescent and contained most protoporphyrin. The amounts present in the cells of different layers progressively decreased from top to bottom of the packed cell column. It is concluded that the protoporphyrin content decreases during the life of the erythrocytes, probably by a process of elution. 3. Although little 59Fe entering the erythrocytes is incorporated into haem, a relationship was observed between iron uptake and protoporphyrin content, which may not be entirely due to aging. This may reflect a mutual dependence of both variables on haem feed-back control. 4. Fluorescence of normoblasts was not detected, indicating that the chief accumulation of porphyrin occurs soon after loss of the nucleus. A hypothesis is suggested to explain these findings.

Breast cancer resistance protein (Bcrp1/Abcg2) is expressed in the harderian gland and mediates transport of conjugated protoporphyrin IX

2007 ◽  
Vol 292 (6) ◽  
pp. C2204-C2212 ◽  
Author(s):  
Johan W. Jonker ◽  
Sandra Musters ◽  
Maria L. H. Vlaming ◽  
Torsten Plösch ◽  
Karin E. R. Gooijert ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Resistance Protein ◽  
Protoporphyrin Ix ◽  
Harderian Gland ◽  
Cancer Resistance ◽  
Erythropoietic Protoporphyria ◽  
Physiological Conditions ◽  
High Affinity ◽  
Expression Site ◽  
Resistance Protein

Proper regulation of intracellular levels of protoporphyrin IX (PPIX), the direct precursor of heme, is important for cell survival. A deficiency in ferrochelatase, which mediates the final step in heme biosynthesis, leads to erythropoietic protoporphyria (EPP), a photosensitivity syndrome caused by the accumulation of PPIX in the skin. We have previously shown that mice with a deficiency in the ABC transporter Bcrp1/Abcg2 display a novel type of protoporphyria. This protoporphyria is mild compared with ferrochelatase-dependent EPP, and in itself not sufficient to cause phototoxicity, but it might exacerbate the consequences of other porphyrias. In this study, we identified the mouse harderian gland as a novel expression site of Bcrp1. Because of its pronounced role in porphyrin secretion, the harderian gland presents a useful tool to study the mechanism of Bcrp1-related protoporphyria and transport of porphyrins. Bcrp1−/− harderian gland displayed a highly increased accumulation of PPIX glycoconjugates, and a similar shift was seen in Bcrp1−/− liver. Tear- and hepatobiliary excretion data suggest that Bcrp1 controls intracellular levels of PPIX by mediating high affinity transport of its glycoconjugates and possibly low-affinity transport of unconjugated PPIX. This mechanism may allow cells to prevent or reduce cytotoxicity of PPIX under excess conditions, without spillage under physiological conditions where PPIX is needed.

scholarly journals Accumulation of protoporphyrin IX from delta-aminolevulinic acid in bovine skin fibroblasts with hereditary erythropoietic protoporphyria. A gene-dosage effect.

1981 ◽  
Vol 153 (5) ◽  
pp. 1094-1101 ◽  
Author(s):  
S Sassa ◽  
S Schwartz ◽  
G Ruth
Keyword(s):  
Aminolevulinic Acid ◽  
Clinical Symptoms ◽  
Gene Dosage ◽  
Protoporphyrin Ix ◽  
Skin Fibroblasts ◽  
Erythropoietic Protoporphyria ◽  
Gene Dosage Effect ◽  
Cultured Fibroblasts ◽  
Clinically Normal ◽  
Stimulation Of

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.

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