Showing papers on "Protoporphyrin IX published in 1990"
TL;DR: In the ongoing clinical trial of ALA-induced Pp IX photodynamic therapy, the response rate for basal cell carcinomas following a single treatment has been 90% complete response and 7.5% partial response for the first 80 lesions treated.
Abstract: 5-Aminolaevulinic acid (ALA) is a precursor of protoporphyrin IX (Pp IX) in the biosynthetic pathway for haem. Certain types of cells have a large capacity to synthesize Pp IX when exposed to an adequate concentration of exogenous ALA. Since the conversion of Pp IX into haem is relatively slow, such cells tend to accumulate photosensitizing concentrations of Pp IX. Pp IX photosensitization can be induced in cells of the epidermis and its appendages, but not in the dermis. Moreover, since ALA in aqueous solution passes readily through abnormal keratin, but not through normal keratin, the topical application of ALA in aqueous solution to actinic keratoses or superficial basal cell or squamous cell carcinomas induces Pp IX photosensitization that is restricted primarily to the abnormal epithelium. Subsequent exposure to photoactivating light selectively destroys such lesions. In our ongoing clinical trial of ALA-induced Pp IX photodynamic therapy, the response rate for basal cell carcinomas following a single treatment has been 90% complete response and 7.5% partial response for the first 80 lesions treated. The cosmetic results have been excellent, and patient acceptance has been very good.
1,546 citations
Journal Article•
TL;DR: The skin of albino mice given 5-aminolevulinic acid by intraperitoneal injection rapidly developed the characteristic red fluorescence of protoporphyrin IX and appeared to recover completely except for a persistent reduction in the number of hair follicles.
Abstract: The skin of albino mice given 5-aminolevulinic acid (ALA) by intraperitoneal injection rapidly developed the characteristic red fluorescence of protoporphyrin IX. Fluorescence microscopy of frozen tissue sections revealed intense red fluorescence within the sebaceous glands and a much weaker fluorescence within the epidermis and hair follicles. Little or no fluorescence was detected in the dermis, blood vessels, or cartilage of the ear. Light microscopy of skin taken at intervals after whole-body exposure of ALA-injected mice to photoactivating light revealed destruction of sebaceous cells, focal epidermal necrosis with a transient acute inflammation, and diffuse reactive changes in the keratinocytes. The dermis showed transient secondary edema and inflammation. The location and severity of the phototoxic damage correlated well with the location and intensity of the red fluorescence. The light-exposed skin appeared to recover completely except for a persistent reduction in the number of hair follicles.
354 citations
TL;DR: The antibody has high affinity for several metalloporphyrins, suggesting an approach to developing antibody-heme catalysts for redox or electron transfer reactions.
Abstract: An antibody elicited to a distorted N-methyl porphyrin catalyzed metal ion chelation by the planar porphyrin. At fixed Zn2+ and Cu2+ concentrations, the antibody-catalyzed reaction showed saturation kinetics with respect to the substrate mesoporphyrin IX (2) and was inhibited by the hapten, N-methylmesoporphyrin IX (1). The turnover number of 80 hour-1 for antibody-catalyzed metallation of 2 with Zn2+ compares with an estimated value of 800 hour-1 for ferrochelatase. The antibody also catalyzed the insertion of Co2+ and Mn2+ into 2, but it did not catalyze the metallation of protoporphyrin IX (3) or deuteroporphyrin IX (4). The antibody has high affinity for several metalloporphyrins, suggesting an approach to developing antibody-heme catalysts for redox or electron transfer reactions.
177 citations
TL;DR: Results indicate that hemin derepresses ferritin synthesis in vitro and that FRP that had been inactivated by hemin remained chemically intact, as revealed by SDS-polyacrylamide gel electrophoresis.
Abstract: Incubation of a 90-kilodalton ferritin repressor protein (FRP), either free or complexed with an L-ferritin transcript, with hemin or Co3+-protoporphyrin IX prevented subsequent repression of ferritin synthesis in a wheat germ extract. Neither FeCl3 in combinations with H2O2, nor Fe3+ or Fe2+ chelated with EDTA, nor Zn2+-protoporphyrin IX, nor protoporphyrin IX caused significant inactivation of FRP. FRP that had been inactivated by hemin remained chemically intact, as revealed by SDS-polyacrylamide gel electrophoresis. Inclusion of chelators of iron or free radical scavengers did not alter the inactivation produced by hemin. These and other results indicate that hemin derepresses ferritin synthesis in vitro.
117 citations
TL;DR: Results indicate that retinol and protoporphyrin IX are bound to the β‐lactoglobulin monomer at two different sites.
109 citations
Journal Article•
TL;DR: The authors propose that ARMD develops as a direct result of photosensitization of the vascular endothelium of the choriocapillaris, Bruch's membrane, and the retinal pigment epithelium by superoxide anion and singlet oxygen generated by photoactive compounds in blood.
Abstract: Age-related macular degeneration (ARMD) is one of the leading causes of severe visual loss in the United States. Numerous risk factors have been investigated, but the pathogenesis of ARMD has remained elusive. The authors propose that ARMD develops as a direct result of photosensitization of the vascular endothelium of the choriocapillaris, Bruch's membrane, and the retinal pigment epithelium (RPE) by superoxide anion and singlet oxygen generated by photoactive compounds in blood. Using electron-spin resonance spectrometry, the free-radical trap, 5,5-dimethyl-1-pyrroline-N-oxide, and the singlet-oxygen trap, 2-(9,10-dimethoxyanthracentyl)-t-butylhydroxylamine, the authors demonstrate that the photoactive compound, protoporphyrin IX (PP IX), a naturally occurring precursor molecule of hemoglobin found in erythrocytes and plasma, generates superoxide anion and singlet oxygen. The amount of reactive-oxygen species produced by this system is dependent on the concentration of PP IX and the intensity and wavelength of the light delivered. Furthermore, the production of these photooxidants is significantly reduced by filtering the excitatory wavelengths of PP IX. These photogenerated oxidants could damage the vascular endothelium of the choriocapillaris, Bruch's membrane, and the RPE, necessitating a reparative process. This could result in features characteristically seen in ARMD such as a thickened Bruch's membrane, RPE atrophy, and hyperplasia. Prevention of phototoxic damage by this mechanism could involve enhancing protective enzymes, increasing scavenger substances, or supplying appropriate filters to eliminate the exciting wavelengths of light.
77 citations
TL;DR: In this paper, the absorption and fluorescence characteristics of PP IX and its complexes with human serum albumin (HSA) and basic proteinoid have been studied in parallel with their photochemical activity.
Abstract: Due to the potential special position of protoporphyrin IX in the evolution of photosynthesis, the absorption and fluorescence characteristics of this pigment and its complexes with human serum albumin (HSA) and basic proteinoid have been studied in parallel with their photochemical activity. The most significant change in the absorption spectrum of PP IX was the appearance of a new maximum at 455 (or 461) nm in the presence of HSA or proteinoid respectively. Some changes in the physicochemical properties of PP IX in different microenvironments have been detected by changes in fluorescence emission and excitation spectra (intensity, quantum yields, position of maxima). The increase of fluorescence quantum yield resulting from the formation of PP IX complexes with HSA or proteinoid correlates with the increase of their photochemical activity. Results obtained are discussed from the point of view of the early evolution of the photosynthetic apparatus.
47 citations
TL;DR: All of the data were consistent with the hypothesis that Proto plays a critical role as a photosensitizing pigment in the mode of action of Protox-inhibiting herbicides and that chlorophyll precursors that are derivatives of Proto are not significantly involved in the Mode of Action of these herbicides.
Abstract: Photobleaching diphenyl ether, cyclic imide and oxadiazole herbicides inhibit protoporphyrinogen oxidase (Protox), resulting in uncontrolled, non-enzymic oxidation of accumulated protoporphyrinogen to protoporphyrin IX (Proto). Proto accumulation is stimulated by deregulation of the porphoyrin pathway due to blockage of heme synthesis. Heme is a Proto product and a feedback inhibitor of δ-aminolevulinic acid synthesis. Strong correlations were found in several species under various conditions (e.g. sprayed on intact plants or taken up by leaf dises) between the accumulation of Proto and the degree of herbicidal damage caused by these herbicides. Levels of protochlorophyllide, Mg-Proto, or Mg-Proto monomethyl ester did not correlate significantly with herbicidal damage. Kinetic data indicated that elevated levels of protochlorophyllide in tissues treated with these herbicides only occurred after Proto had accumulated to high levels. Thus, Proto apparently re-enters the porphyrin pathway to a significant extent after other cellular sites are saturated. Fluorescence microscopy indicated that considerable amounts of Proto accumulated outside the plastid in herbicide-treated cells. All of the data were consistent with the hypothesis that Proto plays a critical role as a photosensitizing pigment in the mode of action of Protox-inhibiting herbicides and that chlorophyll precursors that are derivatives of Proto are not significantly involved in the mode of action of these herbicides.
31 citations
TL;DR: Calculation of the expected ratio of hemin monomers to dimers suggests that the active species is the monomer, and evidence is presented here that this inactivation of FRP is temperature dependent.
27 citations
TL;DR: The total porphyrin content of the two female groups was similar, but enzyme activity in females ovariectomised for 20 weeks significantly decreased, while in castrates (6 weeks) both increased to female levels.
26 citations
TL;DR: In this article, acifluferen-methyl caused electrolyte leakage from L. p. plants after a 2-h lag when treated in white light and when exposed to light, herbicidal damage developed slowly compared with that in plants exposed to both light and herbicide simultaneously.
Abstract: Acifluorfen-methyl caused electrolyte leakage from L. p. plants after a 2-h lag when treated in white light. When treated in darkness for 20 h and then exposed to light, herbicidal damage developed slowly compared with that in plants exposed to light and herbicide simultaneously. In light, acifluorfen-methyl caused an almost 100-fold accumulation of protoporphyrin IX during the first 2 h of treatment, followed by a decline in content. Protochlorophyllide levels in light were decreased by the herbicide. There was no effect on Mg-protoporphyrin IX, coproporphyrin, or uroporphyrin content (...)
TL;DR: The mode of action of 16 peroxidizing herbicides belonging to four different families (diphenyl ethers, oxadiazon, pyridine derivatives, and pyrazole derivatives) has been studied in nonchlorophyllous soybean cell cultures.
TL;DR: The results strongly suggest that ferrochelatase in kidney, liver and erythroid cells can be of one type.
TL;DR: It was concluded that the protoporphyrin-apomyoglobin interactions are capable of organizing the binding site and the unfolded region of the apoprotein into the native holoprotein structure.
Abstract: The structural properties of the complex formed by apomyoglobin and protoporphyrin IX (des-iron myoglobin) were studied to probe the influence of iron-to-histidine coordination on the native myoglobin fold and the heme binding site geometry. Standard two-dimensional proton nuclear magnetic resonance spectroscopy methods were applied to identify porphyrin and protein signals. A pronounced spectral resemblance between carbonmonoxymyoglobin and des-iron myoglobin was noticed that could be exploited to assign a number of resonances by nuclear Overhauser spectroscopy. Protoporphyrin IX was determined to bind in the same orientation as the heme. Most residues in contact with the prosthetic group were found in the holomyoglobin conformation. Several tertiary structure features were also characterized near the protein termini. It was concluded that the protoporphyrin-apomyoglobin interactions are capable of organizing the binding site and the unfolded region of the apoprotein into the native holoprotein structure.
Patent•
25 Jul 1990
TL;DR: In this article, a method of detecting and treating malignant and non-malignant tissue abnormalities and lesions of the skin, conjunctives, respiratory, digestive and vaginal mucosa; endometrium and urothelium in which 5-aminolevulinic acid is administered to the patient in an amount sufficient to induce synthesis of protoporphyrin IX in the leisons.
Abstract: A method of detecting and treating malignant and non-malignant tissue abnormalities and lesions of the skin, conjunctives, respiratory, digestive and vaginal mucosa; endometrium and urothelium in which 5-aminolevulinic acid is administered to the patient in an amount sufficient to induce synthesis of protoporphyrin IX in the leisons, followed by exposure of the treated lesion to a photoactivating light in the range 350-640 nm.
TL;DR: Selective photodecomposition of enzymes by URO I, greater specificity of tumor uptake by U RO I and enhanced porphyrin synthesis by tumors from delta-aminolevulic acid, with predominant formation of UROI, underline the possibility of using Uro I in detection of malignant cells and photodynamic therapy.
Abstract: The action of porphyrins, uroporphyrin I and III (URO I and URO III), pentacarboxylic porphyrin I (PENTA I), coproporphyrin I and III (COPRO I and COPRO III), protoporphyrin IX (PROTO IX) and mesoporphyrin (MESO), on the activity of human erythrocytes δ-aminolevulinic acid dehydratase, porphobilinogenase, deaminase and uroporphyrinogen decarboxylase in the dark and under UV light was investigated. Both photoinactivation and light-independent inactivation was found in all four enzymes using URO I as sensitizer. URO III had a similar action as URO I on porphobilinogenase and deaminase and PROTO IX exerted equal effect as URO I on δ-aminolevulinic acid dehydratase and uroporphyrinogen decarboxylase. Photodynamic efficiency of the porphyrins was dependent on their molecular structure. Selective photodecomposition of enzymes by URO I, greater specificity of tumor uptake by URO I and enhanced porphyrin synthesis by tumors from δ-aminolevulic acid, with predominant formation of URO I, underline the possi...
TL;DR: Some of the porphyrins used in the present study showed an antioxidative effect as did PP, but the others did not show such an effect.
Abstract: The effect of several porphyrins on Fe2+-ascorbic acid-stimulated lipid peroxidation was examined in rat liver homogenates. Not only protoporphyrin IX (PP) but also mesoporphyrin IX and hematoporphyrin inhibited the lipid peroxidation. Some porphyrins, in which 6- and 7- carboxyethyl groups were esterified with a methyl group, such as protoporphyrin IX dimethyl ester and mesoporphyrin IX dimethyl ester, had no antioxidative effect. Hemin and zinc protoporphyrin IX, which are metal-chelated porphyrins, inhibited the lipid peroxidation while cobalt protoporphyrin IX and tin protoporphyrin IX showed no antioxidative effect. Thus, some of the porphyrins used in the present study showed an antioxidative effect as did PP, but the others did not show such an effect.
TL;DR: Results suggest ZnPP may be efficacious in reducing heme catabolism associated with neonatal jaundice and peak neonatal plasma bilirubin concentrations tended to be lower.
Abstract: The effect of zinc (II) protoporphyrin IX (ZnPP) administration (40 mumol/kg, i.v.) on neonatal heme catabolism and the associated bilirubin production was investigated in rhesus (Macaca mulatta) neonates. Carbon monoxide excretion rates (VECO), tissue heme oxygenase activity, and plasma bilirubin concentrations were measured during a 26-hour postnatal period. In ZnPP-treated neonates (n = 4), VECO values were significantly (p = 0.002) diminished by 24% within 24 h. When compared to controls (n = 3), tissue heme oxygenase activity in ZnPP-treated neonates was greatly reduced in both liver (94% inhibition, p = 0.047) and spleen (48% inhibition, p = 0.077), but essentially unaffected in the kidney and brain. Although not statistically significant, peak (24-hour) neonatal plasma bilirubin concentrations tended to be lower (23%). These results suggest ZnPP may be efficacious in reducing heme catabolism associated with neonatal jaundice.
TL;DR: Preliminary data indicate lack of quantitative relationship between inhibition of protoporphyrinogen oxidase, protoprophyrin (IX) formation and peroxidative consequences.
Abstract: Peroxidation is indicated by several physiological parameters: (1) leakage of cell membranes and production of short-chain hydrocarbons, (2) degradation of cell constituents, (3) inhibition of chlorophyll biosynthesis, (4) accumulation of tetrapyrroles (protoporphyrin IX). (5) inhibition of protoporphyrinogen oxidase by peroxidizers, (6) alleviation of peroxidation by inhibitors of chlorophyll biosynthesis. (7) alleviation of peroxidation by photosynthesis inhibitors (“diuron effect”), (8) counteraction of the diuron effect by glucose (heterotrophic conditions). Such parameters, described and elaborated with microalgae and higher plants, arc verified in this study with soybean cells, duckweed and mung beans. Preliminary data indicate lack of quantitative relationship between inhibition of protoporphyrinogen oxidase, protoporphyrin (IX) formation and peroxidative consequences.
TL;DR: Protoporphyrin IX was shown not to be the most common fluorescent pigment in pus and was never present alone, however, the di-carboxylic porphyrins may be produced by bacterial metabolism of its labile vinyl side-chains.
Abstract: Summary
Extracts of 19 samples of pus which showed red fluorescence with ultraviolet light were screened for the presence of porphyrins by absorption spectrophotometry. All those which showed spectra typical of metal-free porphyrins were analysed by high performance liquid chromatography to identify the porphyrins present. These were predominantly the di-carboxylic porphyrins, deuteroporphyrin and mesoporphyrin, and another which was thought to be pemptoporphyrin. This combination matched those reported previously in normal stools. Protoporphyrin IX was shown not to be the most common fluorescent pigment in pus and was never present alone. However, the di-carboxylic porphyrins may be produced by bacterial metabolism of its labile vinyl side-chains. Black-pigmented bacteroides (the melaninogenicus group of Bacteroides spp. and Porphyromonas spp.) were isolated from 12 (63%) of the 19 pus samples; these may produce protoporphyrin IX by the demetallation of haem.
TL;DR: In this article, the authors used rotational correlation times and volumes of the kinetic units within the macromolecules to understand the range of relaxation rates observed for the conjugates.
Abstract: Polymers are finding increasing use in medicine, and conjugates of paramagnetic species and polymers are now being studied as relaxation enhancement agents to improve contrast in magnetic resonance imaging. To assess the potential of such agents, the enhancement of proton relaxation by paramagnetic species bound to macromolecules has been observed for four conjugates of amino acid polymers and manganese (III) protoporphyrin IX. The conjugates all differ in their abilities to enhance the relaxation of water protons in solution; values of relaxation rates range from 3.2 to 9.1 s−1 mM−1. The rotational correlation times and volumes of the kinetic units within the macromolecules have been determined by fluorescence depolarization in an effort to understand the range of relaxation rates observed for the conjugates. The metalloporphyrins bound to the polymers all have very similar dynamic characteristics.
TL;DR: actions of delta-aminolaevulinic acid at alpha 1-adrenoceptor sites are unlikely to be related to the autonomic neuropathy of acute porphyria and it is suggested that ALA is more likely to modify autonomic functions by an indirect action, since it is known at low dose levels to influence GABA-ergic functioning.
Abstract: 1. Pharmacological effects of delta-aminolaevulinic acid (ALA), protoporphyrin IX and haemin were examined in isolated preparations of rabbit jejunum and gastric fundus suspended in oxygenated Ringer-Locke solution at pH 7.0. 2. In jejunal preparations, delta-aminolaevulinic acid (3.0-4.5 mM), protoporphyrin IX (1.1-2.2 mM) and haemin (3.0-4.5 mM) dose-dependently reduced the amplitude of contractions and increased resting length. Pretreatment with prazosin (10(-7) M) inhibited effects produced by delta-aminolaevulinic acid (3 mM) and protoporphyrin IX (1.1 mM) but not those of haemin (3 mM). 3. In fundic preparations, dose-dependent contracture occurred in response to delta-aminolaevulinic acid (0.1-3.0 mM) protoporphyrin IX (0.1-2.2 mM) and haemin (0.6-6.3 mM). Effects qualitatively resembled those of noradrenaline (0.1-0.4 microM). Prazosin (10(-7) M) attenuated these effects, depressing the maximum response and causing a rightward shift of the concentration-response curves. 4. It is concluded that actions of delta-aminolaevulinic acid at alpha 1-adrenoceptor sites are unlikely to be related to the autonomic neuropathy of acute porphyria. Its in vitro effects occurred only at comparatively high concentrations and were mimicked by protoporphyrin IX and haemin. It is suggested that ALA is more likely to modify autonomic functions by an indirect action, since it is known at low dose levels to influence GABA-ergic functioning.
TL;DR: It is shown that both TTMS and PEMS cause mechanism-based inactivation of chick embryo hepatic microsomal cytochrome P-450 and the formation of N-alkylprotoporphyrins in rat liver.
TL;DR: Pharmacological characterization of the Nb2 cell peripheral-type benzodiazepine receptor (PBR) was determined using selected 1,4-benzodiazepines, PK 11195, and protoporphyrin IX (PPIX) to compete for specific Ro5-4864 binding, and data suggest that PPIX possesses an affinity for the N b2 cell PBR.
Journal Article•
TL;DR: It was concluded that the inhibitory effect of carnosine on the ability of the enzyme to be activated by nitroprusside is due to the interaction of Carnosine with guanylate cyclase, and that it is heme directed.
Abstract: Effect of carnosine on the activation of soluble guanylate cyclase by sodium nitroprusside and protoporphyrin IX was studied using human platelet 105000 g supernatants and partially purified heme-deficient guanylate cyclase preparations. In experiments with 105000 g supernatants, carnosine (1 mM) inhibited the enzyme activation by nitroprusside by about 70%. With the partially purified heme-deficient guanylate cyclase, the enzyme activation by nitroprusside was lowered by 86%, and the remaining insignificant stimulatory effect remained unchanged upon carnosine addition. The stimulatory effect of protoporphyrin IX on the partially purified heme-deficient enzyme preparation did not differ from that observed with the 105000 g supernatant; carnosine addition had no effect on activation of guanylate cyclase by protoporphyrin IX. It was concluded that the inhibitory effect of carnosine on the ability of the enzyme to be activated by nitroprusside is due to the interaction of carnosine with guanylate cyclase, and that it is heme directed.
Journal Article•
01 Jan 1990