Characterization of the photoproducts of protoporphyrin IX bound to human serum albumin and immunoglobulin G

Brancaleon, Lorenzo; Magennis, Steven W.; Samuel, Ifor D. W.; Namdas, Ebinazar B.; Lesar, Andrea; Moseley, Harry

doi:10.1016/j.bpc.2003.12.008

Cited by 54 publications

(42 citation statements)

References 17 publications

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“…In addition, the spectral data indicated that the tetrapyrrole ring of hematin was bound to IgG in such a way that one of the planes of the molecule remained fully exposed to the solvent. Our findings are in agreement with previous studies demonstrating that protoporphyrin IX (compound similar to hematin but without iron) is able to bind to Ig molecules (49,50). It was shown in previous studies (49,50) that protoporphyrin binds to Ig molecules in a similar way as was observed for hematin in this study.…”

Section: Mechanisms Of Heme-induced Enlargement Of the Availablesupporting

confidence: 83%

“…Our findings are in agreement with previous studies demonstrating that protoporphyrin IX (compound similar to hematin but without iron) is able to bind to Ig molecules (49,50). It was shown in previous studies (49,50) that protoporphyrin binds to Ig molecules in a similar way as was observed for hematin in this study. Therefore, it seems likely that Igs have an inherent capability to bind heme.…”

Section: Mechanisms Of Heme-induced Enlargement Of the Availablesupporting

confidence: 83%

See 1 more Smart Citation

Antibodies Use Heme as a Cofactor to Extend Their Pathogen Elimination Activity and to Acquire New Effector Functions

Dimitrov

Roumenina

Doltchinkova

et al. 2007

Journal of Biological Chemistry

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Various pathological processes are accompanied by release of high amounts of free heme into the circulation. We demonstrated by kinetic, thermodynamic, and spectroscopic analyses that antibodies have an intrinsic ability to bind heme. This binding resulted in a decrease in the conformational freedom of the antibody paratopes and in a change in the nature of the noncovalent forces responsible for the antigen binding. The antibodies use the molecular imprint of the heme molecule to interact with an enlarged panel of structurally unrelated epitopes. Upon heme binding, monoclonal as well as pooled immunoglobulin G gained an ability to interact with previously unrecognized bacterial antigens and intact bacteria. IgG-heme complexes had an enhanced ability to trigger complement-mediated bacterial killing. It was also shown that heme, bound to immunoglobulins, acted as a cofactor in redox reactions. The potentiation of the antibacterial activity of IgG after contact with heme may represent a novel and inducible innate-type defense mechanism against invading pathogens.

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Section: Mechanisms Of Heme-induced Enlargement Of the Availablesupporting

confidence: 83%

Section: Mechanisms Of Heme-induced Enlargement Of the Availablesupporting

confidence: 83%

Antibodies Use Heme as a Cofactor to Extend Their Pathogen Elimination Activity and to Acquire New Effector Functions

Dimitrov

Roumenina

Doltchinkova

et al. 2007

Journal of Biological Chemistry

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“…FAD and free NADH phasor position are located near the universal circle, but bound NADH is located inside because its lifetime is a combination of more than one exponential (40)(41)(42). The phasor position of protoporphyryn IX (in dimethylformamide and methanol) is located on the universal circle because it is characterized by a single lifetime component (43).…”

Section: Resultsmentioning

confidence: 99%

Phasor approach to fluorescence lifetime microscopy distinguishes different metabolic states of germ cells in a live tissue

Stringari

Cinquin²,

Cinquin³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

374

474

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We describe a label-free imaging method to monitor stem-cell metabolism that discriminates different states of stem cells as they differentiate in living tissues. In this method we use intrinsic fluorescence biomarkers and the phasor approach to fluorescence lifetime imaging microscopy in conjunction with image segmentation, which we use to introduce the concept of the cell phasor. In live tissues we are able to identify intrinsic fluorophores, such as collagen, retinol, retinoic acid, porphyrin, flavins, and free and bound NADH. We have exploited the cell phasor approach to detect a trend in metabolite concentrations along the main axis of the Caenorhabditis elegans germ line. This trend is consistent with known changes in metabolic states during differentiation. The cell phasor approach to lifetime imaging provides a label-free, fit-free, and sensitive method to identify different metabolic states of cells during differentiation, to sense small changes in the redox state of cells, and may identify symmetric and asymmetric divisions and predict cell fate. Our method is a promising noninvasive optical tool for monitoring metabolic pathways during differentiation or disease progression, and for cell sorting in unlabeled tissues.phasor analysis | single cell metabolism T he hallmark of stem cells is their ability to produce a new stem cell by self-renewing, as they generate daughter cells that are committed to differentiation and form specialized tissues (1). The modulation of the balance between self-renewing divisions and differentiation is a central mechanism for stem cells during embryo development, adult tissue regeneration, and homeostasis. Stem-cell differentiation is a complex process mediated both by intrinsic molecular mechanisms and extrinsic signaling. Intrinsic cell polarity, subcellular localization mechanism, asymmetric centrosome and spindles, as well as cell-cycle regulators can establish self-renewing asymmetry during stem-cell division (2, 3). The influence of external chemical and physical stimuli, such as molecular gradients, extracellular matrix remodeling, and niche signaling is crucial for stem-cell plasticity and tissue development (4-6). Extrinsic signals can be propagated through intracellular signal-transduction pathways that converge to genetic networks that control pluripotency. Many different signaling and transcriptional pathways, which are important for development and cell-cycle regulation, converge on regulation of the redox state of stem cells (5,7,8). In turn, histone posttranscriptional modifications and epigenetic mechanisms, such as phosphorylation, acetylation, and methylation, sense cellular metabolism and the variation of metabolites levels (9). Hence, redox balance plays an important role in the maintenance and modulation of stem cell self-renewal and differentiation (10-12).In stem-cell research there is a high demand for noninvasive techniques to investigate self-renewal and differentiation. Methods, such as immunohistochemistry, metabolic assays, and PCR are currently...

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“…Because PpIX usually interact with serum [19], so S180 cells were co-incubated with various concentrations of PpIX in serum-free 1640 medium for 45 min to make sure PpIX rapidly enriched in S180 cells [7], then, serum was added to ensure the PpIX-loading cells in a normal cultural conditions (1640 medium + 10 % serum) for different incubations as specified in the text. For inhibitory study, cyclosporine A (CsA) was added to culture medium 1 h prior to loading PpIX at a final concentration of 0.1 μM.…”

Section: Methodsmentioning

confidence: 99%

DNA Damage and Cell Cycle Arrest Induced by Protoporphyrin IX in Sarcoma 180 Cells

Wang

Zhang

et al. 2013

Cell Physiol Biochem

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Background: Porphyrin derivatives have been widely used in photodynamic therapy as effective sensitizers. Protoporphyrin IX (PpIX), a well-known hematoporphyrin derivative component, shows great potential to enhance light induced tumor cell damage. However, PpIX alone could also exert anti-tumor effects. The mechanisms underlying those direct effects are incompletely understood. This study thus investigated the putative mechanisms underlying the anti-tumor effects of PpIX on sarcoma 180 (S180) cells. Methods: S180 cells were treated with different concentrations of PpIX. Following the treatment, cell viability was evaluated by the 3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide (MTT) assay; Disruption of mitochondrial membrane potential was measured by flow cytometry; The trans-location of apoptosis inducer factor (AIF) from mitochondria to nucleus was visualized by confocal laser scanning microscopy; DNA damage was detected by single cell gel electrophoresis; Cell cycle distribution was analyzed by DNA content with flow cytometry; Cell cycle associated proteins were detected by western blotting. Results: PpIX (≥ 1 µg/ml) significantly inhibited proliferation and reduced viability of S180 cells in a dose-dependent manner. PpIX rapidly and significantly triggered mitochondrial membrane depolarization, AIF (apoptosis inducer factor) translocation from mitochondria to nucleus and DNA damage, effects partially relieved by the specific inhibitor of MPTP (mitochondrial permeability transition pore). Furthermore, S phase arrest and upregulation of the related proteins of P53 and P21 were observed following 12 and 24 h PpIX exposure. Conclusion: PpIX could inhibit tumor cell proliferation by induction of DNA damage and cell cycle arrest in the S phase.

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Characterization of the photoproducts of protoporphyrin IX bound to human serum albumin and immunoglobulin G

Cited by 54 publications

References 17 publications

Antibodies Use Heme as a Cofactor to Extend Their Pathogen Elimination Activity and to Acquire New Effector Functions

Antibodies Use Heme as a Cofactor to Extend Their Pathogen Elimination Activity and to Acquire New Effector Functions

Phasor approach to fluorescence lifetime microscopy distinguishes different metabolic states of germ cells in a live tissue

DNA Damage and Cell Cycle Arrest Induced by Protoporphyrin IX in Sarcoma 180 Cells

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