Erythropoietic protoporphyria and lead intoxication: the molecular basis for difference in cutaneous photosensitivity. I. Different rates of disappearance of protoporphyrin from the erythrocytes, both in vivo and in vitro.

Piomelli, Sergio; Lamola, Angelo A.; Poh-Fitzpatrick, M F; Seaman, Carol; Harber, Leonard C.

doi:10.1172/jci108233

Cited by 141 publications

(59 citation statements)

References 24 publications

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“…[14,[16][17][18] Though the mechanisms involved are not completely elucidated, elevated blood lead levels are associated with impaired haem synthesis [43][44][45] this is unlikely to be the explanation in this study as erythrocyte protoporphyrin activity was similar between Pb workers and controls. Additionally, we previously reported in our observations on the haemopoietic system in this cohort [42] that the haembiosynthetic pathway was uninhibited.…”

Section: Discussionmentioning

confidence: 67%

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Decreased total and ionized calcium levels and haematological indices in occupational lead exposure as evidence of the endocrine disruptive effect of lead

Anetor

Akingbola

Adeniyi

et al. 2005

Indian J Occup Environ Med

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The multisystem and prime environmental and occupational toxin, lead (Pb) is seldom included in the list of endocrine disruptors group like bisphenols A, B and F, nonylphenol, benzoquine, equiline etc. One hundred and thirty-seven subjects consisting of 86 lead workers and 51 unexposed individuals (as controls) participated in the study. Dietary intake including dairy products and micronutrients as assessed by 24-hour dietary recall was similar between lead workers and controls. Calcium homeostasis and haematological indices were evaluated in all subjects. Blood lead level was significantly higher in the lead workers than in controls (P<0.001). Total and ionized calcium levels were in contrast significantly decreased in lead workers compared with controls (P<0.01, P<0.001 respectively). Inorganic phosphate level though slightly raised compared to controls did not reach statistical significance (P>0.05). The haematological indices, haemoglobin, haematocrit, and mean cell haemoglobin concentration like calcium levels were all significantly reduced (P<0.001) in all cases. Semi-quantitative assessment of erythrocyte protoporphyrin was trace (±) in both lead workers and controls (i.e. similar). Serum copper level was significantly higher in Pb workers than in controls (P<0.005). These decreases are consistent with a repression of the endocrine systems regulating both erythropoiesis and calcium homeostasis resident in the proximal convoluted tubule(PCT) of the kidney; the most vulnerable site to Pb damage. Our findings therefore, appear to provide evidence or a reminder that Pb satifies the conditions defining EDCs and should be recognized as one, especially in developing countries where high environmental Pb and malnutrition co-exist and may magnify this effect.

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Section: Discussionmentioning

confidence: 67%

“…[44,45] One of the most likely contributors to this decrement, and the currently most accepted major contributor to this reduction in haematological indices is impaired synthesis of erythropoietin. [14] This glycoprotein hormone regulates both the equilibrium and synthesis of 90% of erythrocytes.…”

Section: Discussionmentioning

confidence: 99%

Decreased total and ionized calcium levels and haematological indices in occupational lead exposure as evidence of the endocrine disruptive effect of lead

Anetor

Akingbola

Adeniyi

et al. 2005

Indian J Occup Environ Med

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“…Gschnait et al (11) have proposed that protoporphyrin in the skin originates from the erythrocytes. It is known that the erythrocyte content of protoporphyrin diminishes as a function of the life time of the erythrocytes (12,13). In the erythrocytes protoporphyrin is probably bound either to heme binding sites on globin (14,15) or to hemoglobin not associated with the heme binding places (16).…”

Section: Introductionmentioning

confidence: 99%

Light-induced protoporphyrin release from erythrocytes in erythropoietic protoporphyria.

Sandberg¹,

Brun²

1982

J. Clin. Invest.

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A B S T R A C T The photohemolysis of normal erythrocytes incubated with protoporphyrin is reduced in the presence of albumin. When globin is added to normal erythrocytes loaded with protoporphyrin, protoporphyrin is bound to globin. During irradiation protoporphyrin moves from globin to the erythrocyte membrane and photohemolysis is initiated.Erythrocytes in patients with erythropoietic protoporphyria contain large amounts of protoporphyrin bound to hemoglobin. Upon irradiation of these cells in the absence of albumin, 40% of protoporphyrin and 80% of hemoglobin is released after 240 kJ/m2. The released protoporphyrin is hemoglobin bound. In contrast, when albumin is present only 8% of hemoglobin is released whereas protoporphyrin is released to 76%. The released protoporphyrin is albumin bound.A hypothesis for the release of erythrocyte protoporphyrin in erythropoietic protoporphyria without simultaneous hemolysis is proposed: Upon irradiation protoporphyrin photodamages its binding sites on hemoglobin, moves through the plasma membrane, and is bound to albumin in plasma.

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“…It is known that Pb exposure is associated with impaired heme synthesis, 4 -6 but even very high blood lead concentrations (BPb) cannot account for the full decrement in hemoglobin (Hgb) synthesis. 5 Pb has other effects on erythrocytes, including inhibition of pyrimidine-5Ј-nucleotidase activity, 7 ineffective erythropoiesis, 8 and shortened red cell survival, 9 -10 but taken together, these still do not account for the effects on Hgb concentration.…”

mentioning

confidence: 99%

A Prospective Study of Prenatal and Childhood Lead Exposure and Erythropoietin Production

Slavkovich¹,

Liu²,

Factor-Litvak³

et al. 2004

Journal of Occupational and Environmental Medicine

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• Summarize what previous studies have shown about the association of blood lead (BPb) concentration, hemoglobin (Hgb), and erythropoietin (EPO) production.• Compare levels of Pb in blood and tibial bone, hemoglobin levels, and EPO production in lead-exposed and unexposed children 4.5 to 12 years of age.• Identify the likely underlying cause of these findings and their implications for lead-exposed children. AbstractWe test the hypothesis that chronic lead (Pb) exposure may be associated with an inability to maintain an adequate serum erythropoietin (EPO) concentration. From a longitudinal study of Pb exposure and infant and childhood development, we measured blood Pb (BPb) and serum EPO concentrations serially at ages 4. 5, 6.5, 9.5, and 12 and tibia (cortical) EPO (J Occup Environ Med. 2004;46:924 -929)

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Erythropoietic protoporphyria and lead intoxication: the molecular basis for difference in cutaneous photosensitivity. I. Different rates of disappearance of protoporphyrin from the erythrocytes, both in vivo and in vitro.

Cited by 141 publications

References 24 publications

Decreased total and ionized calcium levels and haematological indices in occupational lead exposure as evidence of the endocrine disruptive effect of lead

Decreased total and ionized calcium levels and haematological indices in occupational lead exposure as evidence of the endocrine disruptive effect of lead

Light-induced protoporphyrin release from erythrocytes in erythropoietic protoporphyria.

A Prospective Study of Prenatal and Childhood Lead Exposure and Erythropoietin Production

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