Erythropoietic protoporphyria: evidence for multiple sites of excess protoporphyrin formation

Scholnick, Perry L.; Marver, Harvey S.; Schmid, Rudi

doi:10.1172/jci106474

Cited by 84 publications

(35 citation statements)

References 21 publications

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“…Therefore, their antioxidant capacity may be lower, and thus they may remove a higher amount of the produced pro-oxidant protoporphyrin from their system to avoid oxidative damage. According to this hypothesis, females use eggshells as an additional way (apart from feces; Scholnick et al 1971) to remove the potentially harmful protoporphyrin, and the amount of pigment deposited depends on the actual antioxidant capacity of the female. However, we caution that we found no direct evidence for a relationship between shell protoporphyrin concentration and the oxidative status of the female in our study, although oxidative status was estimated during the nestling feeding period, and the level of OXY may have changed between the egg laying and nestling feeding periods (Sepp et al 2012).…”

Section: Eggshell Spotting and Egg Investmentmentioning

confidence: 99%

Darker eggshell spotting indicates lower yolk antioxidant level and poorer female quality in the Eurasian Great Tit (Parus major)

Hargitai

Herényi

Nyíri

et al. 2016

The Auk

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Protoporphyrin pigment causes the red-brown eggshell colors; however, for many species, the function of this pigment is unknown. It has been proposed that eggshell pigmentation may strengthen the shell or that it may be a sexually selected signal, which advertises the quality of the female and that of her offspring to the male parent. In this study, we aimed to discover whether protoporphyrin-based eggshell pigmentation patterns of Eurasian Great Tits (Parus major) were related to female or egg quality. Additionally, we tested whether different methods of eggshell pigmentation estimation could be reliable predictors of eggshell protoporphyrin levels. We found that spot intensity, spot size, spotting coverage, and brown spot chroma indicated the protoporphyrin pigment concentration of the eggshell. Our results revealed that Eurasian Great Tit females that laid eggs with darker pigmentation had more lymphocytes in their circulation and had paler yellow breast and lower UV plumage reflectance, possibly indicating poorer health and individual quality. However, we did not find evidence that eggshell pigmentation patterns indicated the body condition, body size, or plasma oxidative status of females. Furthermore, we found that eggs with darker spots contained lower concentrations of antioxidants in the yolk. High protoporphyrin levels may be detrimental to females as they may cause oxidative damage, and this may be why birds that laid eggs with darker spots deposited lower amounts of antioxidants into the egg yolk. Shell spot darkness may also indicate territory quality, as females that laid smaller clutches also laid eggs with higher eggshell pigmentation levels. Thus, our results suggest that shell spot darkness may indicate the state of health of the female, egg yolk antioxidant level, and possibly also the quality of the territory. Keywords: eggshell color, female condition, lymphocyte count, plumage coloration, protoporphyrin pigmentation, oxidative status, sexual signalling hypothesis Manchas má s oscuras de la cá scara de huevo indican un nivel má s bajo de antioxidantes y una menor calidad de la hembra en Parus major RESUMEN El pigmento protoporfirina causa el color marrón rojizo de la cáscara de huevo; sin embargo, para muchas especies, la función de este pigmento es desconocida. Se ha propuesto que la pigmentación de la cáscara de huevo fortalece la cáscara o que puede ser una señal seleccionada sexualmente, la cual publicita la calidad de la hembra y la de sus polluelos al macho paterno. En este estudio, nuestro objetivo fue determinar si el patrón de pigmentación de la cáscara de huevo basado en protoporfirina de Parus major estuvo relacionado a la calidad de la hembra o del huevo. Además, evaluamos si diferentes métodos de estimación de la pigmentación de la cáscara de huevo podrían ser predictores confiables del nivel de protoporfirina en la cáscara de huevo. Encontramos que la intensidad de las manchas, el tamaño de las manchas, la cobertura de las manchas y el color marrón de las manchas indica...

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Section: Eggshell Spotting and Egg Investmentmentioning

confidence: 99%

Darker eggshell spotting indicates lower yolk antioxidant level and poorer female quality in the Eurasian Great Tit (Parus major)

Hargitai

Herényi

Nyíri

et al. 2016

The Auk

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“…The bone marrow is the predominant source of the excess protoporphyrin, with a variable contribution coming from the liver and other heme-forming tissues (2)(3)(4). The principle clinical manifestation is photosensitivity, which is caused by the photoreactive properties of protoporphyrin circulating in dermal blood vessels and/or deposited in skin (5,6).…”

Section: Introductionmentioning

confidence: 99%

Molecular defects in ferrochelatase in patients with protoporphyria requiring liver transplantation.

Bloomer¹,

Bruzzone²,

Zhu³

et al. 1998

J. Clin. Invest.

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Protoporphyria is a genetic disorder in which a deficiency of mitochondrial ferrochelatase activity causes accumulation of protoporphyrin that produces severe liver damage in some patients. In this study, mutations of the ferrochelatase gene were examined in eight unrelated patients who had liver transplantation. RNA was prepared from liver and/ or lymphoblasts, and specific reverse transcriptase-nested polymerase chain reactions amplified and sequenced ferrochelatase cDNAs. Products shorter than normal resulted from an exon 3 deletion in three patients, exon 10 deletion in two, exon 2 deletion in one, and deletion of five nucleotides in exon 5 in one. Sequence of normal-size products revealed no other mutations. Western blot showed a reduced quantity of normal-size ferrochelatase protein in protoporphyria liver compared with normal liver (19-51%, mean 32% of normal). Levels of the mitochondrial protein F 1 -ATPase ␤ -subunit were not decreased to a similar degree. Liver ferrochelatase activity was reduced more than could be explained by the decrease in ferrochelatase protein (4-20%, mean 9% of normal). These results establish genetic heterogeneity in the most severe phenotype of protoporphyria. However, the gene mutations found share the property of causing a major structural alteration in the ferrochelatase protein.

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“…Since this enhancement only seemed to occur in those experiments in which griseofulvininduced porphyrogenesis was continuously stimulated, it may be speculated that "newer" protoporphyrin in the hepatocyte is more readily mobilized for such accelerated secretion, while "older" deposits are less accessible. Since large amounts of protoporphyrin in livers of patients with protoporphyria are thought to be cleared from the plasma and transported into bile relatively efficiently (as reflected by the large amounts of fecal protoporphyrin excreted daily) (1,3,4,6,8,9,13,15,16,30), an important fraction of total intrahepatic protoporphyrin of these patients may be of such a relatively labile type. Other explanations may be speculated as well.…”

Section: Discussionmentioning

confidence: 99%

“…Partial deficiency of the enzyme heme synthase (8) results in accumulation of protoporphyrin, a hydrophobic heme precursor. In human protoporphyria, the majority of the excess protoporphyrin is produced in the erythron; however, variable contributions to the total may derive from disordered hepatic heme synthesis in different patients (9,10). Protoporphyrin from both sources is excreted by the hepatobiliary-fecal route (11) and undergoes enterohepatic recirculation (12).…”

Section: Introductionmentioning

confidence: 99%

Protoporphyrin hepatopathy. Effects of cholic acid ingestion in murine griseofulvin-induced protoporphyria.

Poh–Fitzpatrick¹,

Sklar²,

Goldsman³

et al. 1983

J. Clin. Invest.

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A B S T R A C T Short-term effects of cholic acid ingestion on hepatic accumulation, fecal excretion, and blood levels of protoporphyrin were studied in vivo in griseofulvin-induced protoporphyric mice. Experimental mice that received feed with 2% griseofulvin and 0.5% cholic acid were compared with control mice that received feed with 2% griseofulvin for 4 wk. Five mice from each group were assessed each week for liver and blood porphyrin levels. Fecal protoporphyrin was compared weekly in the total pooled output of each population. Mean protoporphyrin levels were significantly lower for liver (P < 0.0001), erythrocytes (P < 0.05), and plasma (P < 0.05), and higher for feces (P < 0.001) for the mice that were fed cholic acid. Microscopic protoporphyrin deposits, inflammation, necrosis, and dysplasia were more severe in livers of control mice. A second experimental design compared four regimens in the feed given to all mice after 1-wk induction with 2% griseofulvin: (a) 0.5% cholic acid, (b) no adulterant, (c) 2% griseofulvin and 0.5% cholic acid, and (d) 2% griseofulvin. No difference in protoporphyrin removal from livers of mice in groups 1 and 2 was observed after 1 and 2 wk of these regimens. The apparent reduction in hepatic protoporphyrin content in mice of group 3 as compared with group 4 at weeks 2 and 3 was not significant at P < 0.05.These data suggest that in selected circumstances, Drs. Sklar and Goldsman participated in these studies during student research elective periods at Columbia University College of Physicians and Surgeons. Address all correspondence to Dr. Poh-Fitzpatrick.

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Erythropoietic protoporphyria: evidence for multiple sites of excess protoporphyrin formation

Cited by 84 publications

References 21 publications

Darker eggshell spotting indicates lower yolk antioxidant level and poorer female quality in the Eurasian Great Tit (Parus major)

Darker eggshell spotting indicates lower yolk antioxidant level and poorer female quality in the Eurasian Great Tit (Parus major)

Molecular defects in ferrochelatase in patients with protoporphyria requiring liver transplantation.

Protoporphyrin hepatopathy. Effects of cholic acid ingestion in murine griseofulvin-induced protoporphyria.

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