Protoporphyrin IX-induced structural and functional changes in human red blood cells, haemoglobin and myoglobin.

doi:10.1007/BF02702610

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Protoporphyrin IX-induced structural and functional changes in human red blood cells, haemoglobin and myoglobin.

Journal Article•DOI•

Protoporphyrin IX-induced structural and functional changes in human red blood cells, haemoglobin and myoglobin.

Susmita Sil, Tania Bose, Dibyendu Roy, Abhay Sankar Chakraborti

01 Sep 2004-Journal of Biosciences (J Biosci)-Vol. 29, Iss: 3, pp 281-291

TL;DR: Spectrophotometric studies reveal that protoporphyrin IX interacts with haemoglobin and myoglobin forming ground state complexes, which may have a role in establishing efficacy of therapeutic uses of porphyrins as well as in elucidating their mechanisms of action as therapeutic agents.

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Abstract: Protoporphyrin IX and its derivatives are used as photosensitizers in the photodynamic therapy of cancer. Protoporphyrin IX penetrates into human red blood cells and releases oxygen from them. This leads to a change in the morphology of the cells. Spectrophotometric studies reveal that protoporphyrin IX interacts with haemoglobin and myoglobin forming ground state complexes. For both proteins, the binding affinity constant decreases, while the possible number of binding sites increases, as the aggregation state of the porphyrin is increased. The interactions lead to conformational changes of both haemoglobin and myoglobin as observed in circular dichroism studies. Upon binding with the proteins, protoporphyrin IX releases the heme-bound oxygen from the oxyproteins, which is dependent on the stoichiometric ratios of the porphyrin : protein. The peroxidase activities of haemoglobin and myoglobin are potentiated by the protein-porphyrin complexation. Possible mechanisms underlying the relation between the porphyrin-induced structural modifications of the heme proteins and alterations in their functional properties have been discussed. The findings may have a role in establishing efficacy of therapeutic uses of porphyrins as well as in elucidating their mechanisms of action as therapeutic agents.

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Journal Article•DOI•

Heme cytotoxicity and the pathogenesis of immune-mediated inflammatory diseases.

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Rasmus Larsen¹, Zélia Gouveia¹, Miguel P. Soares¹, Raffaella Gozzelino¹•Institutions (1)

Instituto Gulbenkian de Ciência¹

04 May 2012-Frontiers in Pharmacology

TL;DR: Targeting “free heme” may be used as a therapeutic intervention against diseases related to oxidative stress and immune-mediated inflammatory conditions.

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Abstract: Heme, iron (Fe) protoporphyrin IX, functions as a prosthetic group in a range of hemoproteins essential to support life under aerobic conditions. The Fe contained within the prosthetic heme groups of these hemoproteins can catalyze the production of reactive oxygen species. Presumably for this reason, heme must be sequestered within those hemoproteins, thereby shielding the reactivity of its Fe-heme. However, under pathologic conditions associated with oxidative stress, some hemoproteins can release their prosthetic heme groups. While this heme is not necessarily damaging per se, it becomes highly cytotoxic in the presence of a range of inflammatory mediators such as tumor necrosis factor. This can lead to tissue damage and, as such, exacerbate the pathologic outcome of several immune-mediated inflammatory conditions. Presumably, targeting “free heme” may be used as a therapeutic intervention against these diseases.

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94 citations

Cites background from "Protoporphyrin IX-induced structura..."

...A number of factors can contribute to this (Kempe et al., 2007; Lang et al., 2008), including deregulated plasma osmolarity, acidosis, bacterial hemolysins (particularly Clostridium perfringens; Gutierrez et al., 1995), or free heme itself (Sil et al., 2004)....
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Journal Article•DOI•

Characterization of a Mycobacterium tuberculosis Nanocompartment and Its Potential Cargo Proteins

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Heidi Contreras, Matthew S. Joens¹, Lisa M. McMath, Vincent P. Le, Michael V. Tullius², Jacqueline M. Kimmey², Neda Bionghi², Marcus A. Horwitz², James A. J. Fitzpatrick¹, Celia W. Goulding³ - Show less +6 more•Institutions (3)

Salk Institute for Biological Studies¹, University of California, Los Angeles², University of California, Irvine³

27 Jun 2014-Journal of Biological Chemistry

TL;DR: It is shown by co-purification and electron microscopy that mycobacteria via Mt-Enc can encapsulate Mt-DyP, Mt-BfrB, and Mt-FolB, which may aid in detoxification of the local environment to ensure long term survival.

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82 citations

Cites methods from "Protoporphyrin IX-induced structura..."

...Heme (23) and PPIX (24) solutions were freshly prepared prior to each experiment....
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...JUNE 27, 2014 • VOLUME 289 • NUMBER 26 JOURNAL OF BIOLOGICAL CHEMISTRY 18283 Although Mt-DyP has heme-dependent peroxidase activity, Mt-DyP deferrochelatase activity was also tested because we have shown that Mt-DyP can bind PPIX (Fig....
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...Crystals of PPIX were dissolved in 150 mM NaCl, vortexed periodically over 20 min, and centrifuged....
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...Heme and PPIX solutions were protected from light and used within 12 h. Micromolar increments of either heme or PPIX were titrated into either 5 or 2.5 M purified apo-Mt-DyP, respectively, in 50 mM Tris-HCl (pH 7.4) and 150 mM NaCl....
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...Finally, Mt-DyP 18282 JOURNAL OF BIOLOGICAL CHEMISTRY VOLUME 289 • NUMBER 26 • JUNE 27, 2014 bound both heme and PPIX (Fig....
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Journal Article•DOI•

Pulmonary Proteases in the Cystic Fibrosis Lung Induce Interleukin 8 Expression from Bronchial Epithelial Cells via a Heme/Meprin/Epidermal Growth Factor Receptor/Toll-like Receptor Pathway

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Sonya Cosgrove¹, Sanjay H. Chotirmall¹, Catherine M. Greene¹, Noel G. McElvaney¹•Institutions (1)

Royal College of Surgeons in Ireland¹

04 Mar 2011-Journal of Biological Chemistry

TL;DR: It is shown that the Pseudomonas proteases and the neutrophil proteases (neutrophil elastase (NE) and proteinase-3) are capable of almost complete degradation of hemoglobin in vitro but that NE is the predominant protease that cleaves hemoglobinIn vivo in CF bronchoalveolar lavage fluid.

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63 citations

Journal Article•DOI•

Role of the c-Jun N-terminal kinase signaling pathway in SW480 cell apoptosis in response to 5-aminolevulinic acid-based photodynamic therapy

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Jiang-Hua Zheng, Kai Chen, Zu-Lin Chen

01 Jan 2008-World Chinese Journal of Digestology

62 citations

Journal Article•DOI•

Enhancement techniques for improving 5-aminolevulinic acid delivery through the skin

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Li-Wen Zhang¹, Yi-Ping Fang², Jia-You Fang³, Jia-You Fang¹•Institutions (3)

Chang Gung University¹, Yuanpei University², King Saud University³

01 Mar 2011-Dermatologica Sinica

TL;DR: Enhanced delivery systems for ALA in the skin will play an important role in ALA-PDT, and several enhancement techniques for increasing ALA permeation through the skin are introduced.

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46 citations

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References

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Book•

Photodynamic Therapy

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C.J. Gomer

01 May 1988

TL;DR: A comprehensive review of mechanisms of subcellular and tumor localization of photosensitizing agents, as well as of molecular, cellular, and tumor responses associated with photodynamic therapy, are discussed.

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Abstract: Photodynamic therapy involves administration of a tumor-localizing photosensitizing agent, which may require metabolic synthesis (i.e., a prodrug), followed by activation of the agent by light of a specific wavelength. This therapy results in a sequence of photochemical and photobiologic processes that cause irreversible photodamage to tumor tissues. Results from preclinical and clinical studies conducted worldwide over a 25-year period have established photodynamic therapy as a useful treatment approach for some cancers. Since 1993, regulatory approval for photodynamic therapy involving use of a partially purified, commercially available hematoporphyrin derivative compound (Photofrin) in patients with early and advanced stage cancer of the lung, digestive tract, and genitourinary tract has been obtained in Canada, The Netherlands, France, Germany, Japan, and the United States. We have attempted to conduct and present a comprehensive review of this rapidly expanding field. Mechanisms of subcellular and tumor localization of photosensitizing agents, as well as of molecular, cellular, and tumor responses associated with photodynamic therapy, are discussed. Technical issues regarding light dosimetry are also considered.

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4,580 citations

Journal Article•DOI•

Determination of the secondary structures of proteins by circular dichroism and optical rotatory dispersion.

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Yee-Hsiung Chen, Jen Tsi Yang, Hugo M. Martinez

24 Oct 1972-Biochemistry

1,853 citations

"Protoporphyrin IX-induced structura..." refers methods in this paper

...The αhelical contents of the protein in the presence and absence of the porphyrin were estimated from the spectra according to the relation (Chen et al 1972): Fraction of α-helix = ([θ ]222 + 2340)/– 30300, where [θ ]222 is the ellipticity at 222 nm. 2.9 Assay of peroxidase activities of Hb and…...
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Porphyrins and metalloporphyrins.

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Kevin M. Smith

01 Jan 1975

1,757 citations

Journal Article•DOI•

Biological effects of the superoxide radical.

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Irwin Fridovich¹•Institutions (1)

Duke University¹

15 May 1986-Archives of Biochemistry and Biophysics

TL;DR: Can the superoxide radical exert deleterious effects independent of participating with H2O2 in the production of the hydroxyl radical?

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1,433 citations

"Protoporphyrin IX-induced structura..." refers background in this paper

...Superoxide radicals are generated in HRP/H2O2/NAD(P)H system (Takayama and Nakano 1977) and these radicals may inhibit the peroxidase activity of HRP (Fridovich 1986)....
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...…radicals are generated in HRP/H2O2/NAD(P)H system (Takayama and Nakano 1977) and these radicals may inhibit the peroxidase activity of HRP (Fridovich 1986). van Steveninck et al (1987, 1988) have postulated that superoxide radical generation is prevented by the porphyrin hematoporphyrin…...
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...Interaction of PP with HRP as demonstrated from this laboratory (Sil and Chakraborti 1997) may be involved in this process, because potentiation of HRP activity has a positive correlation with the extent of binding of the protein with the porphyrin....
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...Drug-protein binding; haemoglobin; myoglobin; protoporphyrin IX; red blood cells ________________ Abbreviations used: cd, Circular dichroism; EPP, erythropoietic protoporphyria; Hb, haemoglobin; HRP, horseradish peroxidase; Mb, oxymyoglobin; PDT, photodynamic therapy; PP, protoporphyrin; RBC, red blood cells; ZPP, zinc protoporphyrin....
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...It is not yet known how porphyrins remove or inhibit generation of superoxide radicals in HRP system....
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Journal Article•DOI•

5-Aminolevulinic acid-based photodynamic therapy. Clinical research and future challenges.

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Qian Peng¹, Trond Warloe¹, Kristian Berg¹, Johan Emelian Moan¹, Magne Kongshaug¹, Karl Erik Giercksky¹, Jahn M. Nesland¹ - Show less +3 more•Institutions (1)

University of Oslo¹

15 Jun 1997-Cancer

TL;DR: Studies have shown that a higher accumulation of ALA‐derived PpIX in rapidly proliferating cells may provide a biologic rationale for clinical use of ALa‐based PDT and diagnosis, however, no review updating the clinical data has appeared so far.

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Abstract: BACKGROUND Photodynamic therapy (PDT) for cancer patients has developed into an important new clinical treatment modality in the past 25 years PDT involves administration of a tumor-localizing photosensitizer or photosensitizer prodrug (5-aminolevulinic acid [ALA], a precursor in the heme biosynthetic pathway) and the subsequent activation of the photosensitizer by light Although several photosensitizers other than ALA-derived protoporphyrin IX (PpIX) have been used in clinical PDT, ALA-based PDT has been the most active area of clinical PDT research during the past 5 years Studies have shown that a higher accumulation of ALA-derived PpIX in rapidly proliferating cells may provide a biologic rationale for clinical use of ALA-based PDT and diagnosis However, no review updating the clinical data has appeared so far METHODS A review of recently published data on clinical ALA-based PDT and diagnosis was conducted RESULTS Several individual studies in which patients with primary nonmelanoma cutaneous tumors received topical ALA-based PDT have reported promising results, including outstanding cosmetic results However, the modality with present protocols does not, in general, appear to be superior to conventional therapies with respect to initial complete response rates and long term recurrence rates, particularly in the treatment of nodular skin tumors Topical ALA-PDT does have the following advantages over conventional treatments: it is noninvasive; it produces excellent cosmetic results; it is well tolerated by patients; it can be used to treat multiple superficial lesions in short treatment sessions; it can be applied to patients who refuse surgery or have pacemakers and bleeding tendency; it can be used to treat lesions in specific locations, such as the oral mucosa or the genital area; it can be used as a palliative treatment; and it can be applied repeatedly without cumulative toxicity Topical ALA-PDT also has potential as a treatment for nonneoplastic skin diseases Systemic administration of ALA does not seem to be severely toxic, but the advantage of using this approach for PDT of superficial lesions of internal hollow organs is still uncertain The ALA-derived porphyrin fluorescence technique would be useful in the diagnosis of superficial lesions of internal hollow organs CONCLUSIONS Promising results of ALA-based clinical PDT and diagnosis have been obtained The modality has advantages over conventional treatments However, some improvements need to be made, such as optimization of parameters of ALA-based PDT and diagnosis; increased tumor selectivity of ALA-derived PpIX; better understanding of light distribution in tissue; improvement of light dosimetry procedure; and development of simpler, cheaper, and more efficient light delivery systems Cancer 1997; 79:2282-308 © 1997 American Cancer Society

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1,000 citations