Mechanistic studies on uroporphyrin I-induced photoinactivation of some heme-enzymes

Afonso, Susana; Polo, César F.; Salamanca, Rafael Enrı́quez de; Batlle, Alcira

doi:10.1016/1357-2725(95)00159-x

Cited by 21 publications

(7 citation statements)

References 14 publications

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“…In the presence of either catalase or GSH, enzyme photoinactivation was lower than in their absence, while ethanol, glucose and dimethyl sulfoxide prevented the URO I-induced photoinactivation ( Figure 4) (44). These results indicate that a type I mechanism would be the main reaction through which the porphyrin exerts its photodynamic action, involving hydrogen peroxide and hydroxyl radicals, although singlet oxygen-mediated reactions (type II) could be produced simultaneously, contributing to enzyme photoinactivation yet to a much lesser extent (44). Preincubation with superoxide dismutase did not protect any of the four enzymes from inactivation ( Figure 4) (44) …”

Section: Light-dependent and Light-independent Enzyme Inactivationmentioning

confidence: 99%

“…To investigate the mechanism of photoinactivation induced by URO I, ALA-D, PBGase, PBG-D and URO-D were preincubated in the presence of specific scavengers for the different ROS and then exposed to the porphyrin and UV light, in an aerobic atmosphere (44). The presence of histidine or sodium azide did not protect the enzymes against the effect of URO I (Figure 4) (44); however, generation of singlet oxygen was detected during the treatment of PBG-D with URO I (Afonso SG, Enríquez de Salamanca …”

Section: Mechanisms Of Photodynamic Actionmentioning

confidence: 99%

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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: Light-dependent and Light-independent Enzyme Inactivationmentioning

confidence: 99%

Section: Mechanisms Of Photodynamic Actionmentioning

confidence: 99%

The photodynamic and non-photodynamic actions of porphyrins

Afonso

Salamanca

Batlle

1999

Braz J Med Biol Res

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“…Haem-compounds are necessary as a growth factor for the parasite. (Afonso et al 1996 ;Kumar and Bandyopadhyay, 2005), it was of interest to investigate the effect of haemin on the growth of T. cruzi. Because high levels of haemin and related porphyrins have an important cytotoxic action through the generation of reactive oxygen species (ROS) such as superoxide anion (O 2 x ), hydrogen peroxide (H 2 O 2 ) and the highly reactive hydroxyl radical (OH . )…”

Section: Introductionmentioning

confidence: 99%

Effect of haemin on growth, protein content and the antioxidant defence system inTrypanosoma cruzi

et al. 2007

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A nutritional characteristic of trypanosomatid protozoa is that in vitro they need a haem-compound as a growth factor, which is supplied as haemoglobin, haematin or haemin. Because haemin and related porphyrins are an important source of oxidative stress in biological systems, the effect of haemin on growth, protein content and the antioxidant defence system in Trypanosoma cruzi was evaluated. We have observed that, in epimastigotes grown under different haemin concentrations in the culture medium (0-30 mg/l), 5 mg/l was the haemin concentration yielding optimum growth. Above 15 mg/l there was a clear decrease in growth rate, producing the epimastigote to amastigote transformation. Such morphological change was observed together with a marked injury of the enzymatic machinery of the parasite, leading to diminished protein synthesis as well as lower activity of the antioxidant enzymes (superoxide dismutase, ascorbate peroxidase and trypanothione reductase), reduced total thiol content and a marked increase in the HaemOx-1 activity and expression. The current work demonstrates that there is a correlation between higher haemin concentrations in the culture medium and oxidative damage in the cells. Under these conditions induction of HaemOx-1 would indicate the important role of this enzyme as an antioxidant defence response in Trypanosoma cruzi.

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“…Whether this Snitrosation affects Pantophysin's role in GLUT translocation is expected for further research. (D) Aminolevulinate delta dehydratase (ALAD), its activity decreased in the liver of high glucose-induced diabetic rats (Folmer et al, 2002) and the oxidation of cysteines is thought to be one possible reason (Afonso et al, 1996). Here we found that S-nitrosation of ALAD increased 2.17 folds in diabetic mouse liver, suggesting one possible contribution to the decrease of ALAD activity.…”

Section: Discussionmentioning

confidence: 66%

Quantitative proteomic analysis of S-nitrosated proteins in diabetic mouse liver with ICAT switch method

et al. 2010

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In this study we developed a quantitative proteomic method named ICAT switch by introducing isotope-coded affinity tag (ICAT) reagents into the biotin-switch method, and used it to investigate S-nitrosation in the liver of normal control C57BL/6J mice and type 2 diabetic KK-Ay mice. We got fifty-eight S-nitrosated peptides with quantitative information in our research, among which thirty-seven had changed S-nitrosation levels in diabetic mouse liver. The S-nitrosated peptides belonged to fortyeight proteins (twenty-eight were new S-nitrosated proteins), some of which were new targets of S-nitrosation and known to be related with diabetes. S-nitrosation patterns were different between diabetic and normal mice. Gene ontology enrichment results suggested that S-nitrosated proteins are more abundant in amino acid metabolic processes. The network constructed for Snitrosated proteins by text-mining technology provided clues about the relationship between S-nitrosation and type 2 diabetes. Our work provides a new approach for quantifying S-nitrosated proteins and suggests that the integrative functions of S-nitrosation may take part in pathophysiological processes of type 2 diabetes.

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Mechanistic studies on uroporphyrin I-induced photoinactivation of some heme-enzymes

Cited by 21 publications

References 14 publications

The photodynamic and non-photodynamic actions of porphyrins

The photodynamic and non-photodynamic actions of porphyrins

Effect of haemin on growth, protein content and the antioxidant defence system inTrypanosoma cruzi

Quantitative proteomic analysis of S-nitrosated proteins in diabetic mouse liver with ICAT switch method

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