Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The porphyrias are the only group of diseases caused by endogenous phototoxic agents. While patients with erythropoietic protoporphyria and those with porphyria cutanea tarda both have skin lesions on sun-exposed areas, there are differences in their cutaneous manifestations. Based on information discussed in this chapter, the following pathophysiologic mechanisms can be proposed. In porphyria cutanea tarda, photoactivation of the complement system in the presence of uroporphyrin results in activation of dermal mast cells, which release their proteases. This results in dermal-epidermal separation, reflected clinically as skin fragility and vesicles. The interaction between activated mast cells with fibroblasts, the nature of which is still unclear, may contribute to fibrosis and sclerodermoid skin changes. The stimulatory effect of uroporphyrin on collagen biosynthesis by fibroblasts, which occurs independent of irradiation, may be responsible for the sclerodermoid lesions seen at sun-exposed as well as sun-protected areas. In erythropoietic protoporphyria, mast cell activation can occur as the result of complement activation induced by protoporphyrin and irradiation. Protoporphyrin and irradiation may also directly induce the release of preformed and generated mediators from mast cells, a process mediated at least in part by peroxidation. The release of mast cell mediators may account for the erythema, edema, and urticaria observed in patients with erythropoietic protoporphyria upon exposure to sunlight. Interaction of mast cells with fibroblasts, and the direct membrane-damaging effect of protoporphyrin and irradiation on the latter, may contribute to the waxy thickening of skin seen in chronically sun-exposed areas of these patients. There are, however, many unanswered questions. What accounts for the different biological effects of mast cell-derived mediators: dermal-epidermal separation in one, erythema and urticaria in the other? The fragmentation of dermal collagen bundles associated with cleavage beneath the lamina densa, and the hyperpigmentation and hypertrichosis observed in some patients with porphyria cutanea tarda remain unexplained. What is the mechanism of the reduplication of blood vessel basal lamina in the non-sun-exposed areas of both types of patient? Are there any roles for cytokines and epidermal cell-derived eicosanoids? While it is clear that the pathogenesis of cutaneous lesions in porphyria cutanea tarda and erythropoietic protoporphyria involves interactions among inflammatory mediators and various cells in skin, much still needs to be done to further our understanding of their pathophysiology.
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PMID:Mechanisms of phototoxicity in porphyria cutanea tarda and erythropoietic protoporphyria. 248 74

It has been shown that treatment of rat peritoneal mast cells with protoporphyrin plus long-wave ultraviolet light (UVA) irradiation can suppress mediator secretion. In this study we conducted a morphometric and ultrastructural analysis of rat peritoneal mast cells to investigate possible alterations produced by this treatment before or after stimulation with calcium ionophore. Protoporphyrin plus UVA, at doses causing inhibition of mediator release, had no effect on either cell size or viability but increased cellular sphericity. There was a 43% reduction of the cell surface area, and qualitative inspection of the cells revealed that this change was associated with a reduction in microfolds on the cell surface. After 1 minute of incubation with calcium ionophore A23187 (1 mumol/L), both cells that were pretreated with protoporphyrin plus UVA and control cells showed dramatic changes in granule structure. Although treated cells had an unchanged tendency to have granules that closely approached the plasma membrane, there was an inhibition of granule extrusion in response to ionophore stimulation. These observations may be relevant to the inhibitory effect of protoporphyrin plus UVA on the generation and release of mast cell mediators.
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PMID:Inhibition of mast cell mediator secretion induced by protoporphyrin plus long-wave ultraviolet light: a morphometric and ultrastructural analysis. 818 33

Mechanisms of relaxation and contraction to protease-activated receptor- (PAR) tethered ligand peptides (SFLLRN/TFLLR, SLIGRL and GYPGKF (all C-terminally amidated) for PAR1, PAR2 and PAR4, respectively) and enzymes (thrombin and trypsin) were investigated in isolated segments of rat trachea, main and first order intrapulmonary bronchi. In airway segments previously exposed to SLIGRL, SFLLRN caused contractions that were potentiated by indomethacin, but were independent of mast cell degranulation. Contractions to TFLLR in the intrapulmonary bronchi were similarly potentiated by indomethacin. SLIGRL caused epithelium-dependent relaxations which were unaffected by N(G)-nitro-L-arginine, 1-H-oxodiazol-[1,2,4]-[4,3-a]quinoxaline-1-one or zinc-protoporphyrin-IX but were abolished by haemoglobin in all three regions of the airways. Relaxations to SLIGRL were markedly attenuated by indomethacin only in the main and intrapulmonary bronchi. GYPGKF caused epithelium-dependent relaxations in all three regions of the airway which were only significantly inhibited by indomethacin in the intrapulmonary bronchi. In general, thrombin and trypsin failed to cause any response in the airways tested. Intense PAR2-immunoreactivity was observed on airway epithelium. PAR1-immunoreactivity was faint on airway epithelium and smooth muscle, but was prevalent in mast cells. These findings indicate that PAR2 and possibly PAR4 present on rat airway epithelia mediate smooth muscle relaxation via cyclo-oxygenase-dependent and -independent mechanisms. PAR1-mediated contractions were most likely due to activation of smooth muscle receptors. The general failure of thrombin and trypsin to cause responses which may have been due to endogenous protease inhibitors, highlights the need for caution in assessing pathophysiological roles for PARs if only enzymes are used to activate PARs.
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PMID:Effect of protease-activated receptor (PAR)-1, -2 and -4-activating peptides, thrombin and trypsin in rat isolated airways. 1113 35