Exogenous protoporphyrin inhibits Hep G2 cell proliferation, increases the intracellular hydrogen peroxide concentration and causes ultrastructural alterations

Koningsberger, J. C.; Rademakers, L. H. P. M.; Hattum, Jan van; Faille, H. Baart de la; Wiegman, L. J. J. M.; Italiaander, Erna; Henegouwen, G. P. van Berge; Marx, Jean L.

doi:10.1016/0168-8278(95)80260-6

Cited by 31 publications

(19 citation statements)

References 25 publications

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“…Decreased cytochrome c oxidase activity and increased · OH lactate production and glucose utilization were induced by porphyrin derivatives in cell cultures (34). The potentiating action of hematoporphyrin on the horseradish peroxidase-catalyzed oxidation of NADPH in the dark has been demonstrated (35,36), and the interaction of PROTO with redox systems such as the Haber-Weiss and Fenton reactions, possibly yielding an electronically excited porphyrin, has also been observed in the dark (37). However, there is still much to learn about the reactivity of tetrapyrroles in the dark.…”

Section: Photodynamic and Non-photodynamic Actionmentioning

confidence: 92%

The photodynamic and non-photodynamic actions of porphyrins

Afonso

Salamanca

Batlle

1999

Braz J Med Biol Res

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Porphyrias are a family of inherited diseases, each associated with a partial defect in one of the enzymes of the heme biosynthetic pathway. In six of the eight porphyrias described, the main clinical manifestation is skin photosensitivity brought about by the action of light on porphyrins, which are deposited in the upper epidermal layer of the skin. Porphyrins absorb light energy intensively in the UV region, and to a lesser extent in the long visible bands, resulting in transitions to excited electronic states. The excited porphyrin may react directly with biological structures (type I reactions) or with molecular oxygen, generating excited singlet oxygen (type II reactions). Besides this well-known photodynamic action of porphyrins, a novel light-independent effect of porphyrins has been described. Irradiation of enzymes in the presence of porphyrins mainly induces type I reactions, although type II reactions could also occur, further increasing the direct non-photodynamic effect of porphyrins on proteins and macromolecules. Conformational changes of protein structure are induced by porphyrins in the dark or under UV light, resulting in reduced enzyme activity and increased proteolytic susceptibility. The effect of porphyrins depends not only on their physico-chemical properties but also on the specific site on the protein on which they act. Porphyrin action alters the functionality of the enzymes of the heme biosynthetic pathway exacerbating the metabolic deficiencies in porphyrias. Light energy absorption by porphyrins results in the generation of oxygen reactive species, overcoming the protective cellular mechanisms and leading to molecular, cell and tissue damage, thus amplifying the porphyric picture.

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Section: Photodynamic and Non-photodynamic Actionmentioning

confidence: 92%

The photodynamic and non-photodynamic actions of porphyrins

Afonso

Salamanca

Batlle

1999

Braz J Med Biol Res

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“…This means that the erythroid cells of these animals had a longer life due to less direct porphyrin toxicity and less destruction of maturing corrected RBC. In this way, Koningsberger et al 29 provided evidence that protoporphyrin can induce the generation of oxygen-free radicals, in particular hydrogen peroxide, which can yield OH radicals in iron/copper-driven Fenton chemistry. The latter compounds are a very potent oxidant; they are able to initiate a chain reaction of lipid peroxidation, to disturb the structure and function of cellular membranes and to reduce the life RBC.…”

Section: Discussionmentioning

confidence: 99%

Successful therapeutic effect in a mouse model of erythropoietic protoporphyria by partial genetic correction and fluorescence-based selection of hematopoietic cells

Fontanellas

Méndez²,

Mazurier³

et al. 2001

Gene Ther

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“…Other studies have reported on the toxic potential of PP-IX in absence of light. For example, treatment of HepG2 cells with PP-IX led to a dose-dependent decrease in proliferation in absence of light (26). Additionally, there are reports of one-electron reduction of porphyrins to the respective anion-free radicals by hepatic microsomal enzymes (27,28).…”

Section: Protein Aggregation As a Mechanism Of Cell Injury Inmentioning

confidence: 99%

Ambient Light Promotes Selective Subcellular Proteotoxicity after Endogenous and Exogenous Porphyrinogenic Stress

Maitra

Elenbaas

Whitesall

et al. 2015

Journal of Biological Chemistry

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Background: Protoporphyria causes mouse liver damage in association with lamin aggregation. Results: Endogenously and exogenously stimulated protoporphyrin-IX accumulation leads to ambient light-triggered organelle-selective protein aggregation, ultrastructural alterations, ER stress, and proteasome inhibition. Conclusion: External and internal porphyrinogenic stress cause compartment-selective proteotoxic damage and protein aggregation. Significance: Subcellular compartment-specific and porphyrin-selective protein aggregation may be a hallmark injury mechanism in porphyrias.

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Exogenous protoporphyrin inhibits Hep G2 cell proliferation, increases the intracellular hydrogen peroxide concentration and causes ultrastructural alterations

Cited by 31 publications

References 25 publications

The photodynamic and non-photodynamic actions of porphyrins

The photodynamic and non-photodynamic actions of porphyrins

Successful therapeutic effect in a mouse model of erythropoietic protoporphyria by partial genetic correction and fluorescence-based selection of hematopoietic cells

Ambient Light Promotes Selective Subcellular Proteotoxicity after Endogenous and Exogenous Porphyrinogenic Stress

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