The Experts below are selected from a list of 198 Experts worldwide ranked by ideXlab platform
Genji Imokawa - One of the best experts on this subject based on the ideXlab platform.
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Recent advances in characterizing biological mechanisms underlying UV-induced wrinkles: A pivotal role of fibrobrast-derived Elastase
Archives of Dermatological Research, 2008Co-Authors: Genji ImokawaAbstract:In clinical studies, the formation of facial wrinkles has been closely linked to the loss of elastic properties of the skin. Cumulative irradiation with ultraviolet (UV) B at suberythemal doses significantly reduces the elastic properties of the skin, resulting in the formation of wrinkles. In in vitro studies, we identified a paracrine pathway between keratinocytes and fibroblasts, which leads to wrinkle formation via the up-regulation of fibroblast Elastases that degrade elastic fibers. UVB irradiation stimulates the activity of fibroblast Elastases in animal skin. Scanning electron microscopy revealed that cumulative UVB irradiation elicits a marked alteration in the three-dimensional structure of elastic fibers, which is closely associated with the subsequent reduction in the elastic properties of the skin, resulting in wrinkle formation. Studies using anti-wrinkle treatments suggest a close relationship between the recovery of wrinkles and an improvement in the linearity of elastic fibers. Those studies also suggest a close correlation between the recovery in the linearity of elastic fibers and the improvement in skin elasticity. In a study using ovariectomized animals, we characterized the important role of Elastase in their high vulnerability to UV-induced wrinkle formation. A synthetic inhibitor specific for fibroblast Elastases significantly prevents wrinkle formation without reducing the elastic properties of the skin, accompanied by minor damage in elastic fibers. Finally, we identified an effective extract of Zingiber officinale (L.) Rose from a screen of many herb extracts, which has a safe and potent inhibitory activity against fibroblast Elastases. Animal studies using the L. Rose extract revealed that it has significant preventive effects against UVB-induced wrinkle formation, which occur in concert with beneficial effects on skin elasticity. A 1-year clinical study on human facial skin to determine the efficacy of the L. Rose extract demonstrated that it inhibits the UV-induced decrease in skin elasticity and prevents or improves wrinkle formation in skin around the corner of the eye without changing the water content of the stratum corneum. Our long-term studies support our hypothesis for a mechanism of wrinkle formation in which cytokine expression is activated by UV irradiation and triggers dermal fibroblasts to increase the expression of Elastase. That increase in Elastase results in the deterioration of the three-dimensional architecture of elastic fibers, reducing skin elasticity and finally leading to the formation of wrinkles.
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the role of Elastases secreted by fibroblasts in wrinkle formation implication through selective inhibition of Elastase activity
Photochemistry and Photobiology, 2001Co-Authors: Naoko Tsuji, Shigeru Moriwaki, Yasuto Suzuki, Yoshinori Takema, Genji ImokawaAbstract:Abstract We have previously demonstrated that decreases in skin elasticity, accompanied by increases in the tortuosity of elastic fibers, are important early events in wrinkle formation. In order to study the role of Elastases in the degeneration of elastic fibers during wrinkle formation we examined the effects of an inhibitor of skin fibroblast Elastase, N-phenethylphosphonyl-l-leucyl-l-tryptophane (NPLT), on wrinkle formation in hairless mice skin following UV irradiation. Dorsal skins of hairless mice were exposed daily to UV light for 18 weeks at doses of 65–95 mJ/cm2 and treated topically with 100 μL of 1 mM NPLT immediately after each UV irradiation. Wrinkles on dorsal skins were evaluated from week 6 through week 18. The daily exposure of mouse skin to UV light with less than 1 minimal erythemal dose significantly enhanced the activity of Elastase in the exposed skin by week 4, and the elevated levels of Elastase activity were significantly reduced by the in vitro incubation with NPLT in a dose-de...
Enno Christophers - One of the best experts on this subject based on the ideXlab platform.
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elafin an Elastase specific inhibitor of human skin purification characterization and complete amino acid sequence
Journal of Biological Chemistry, 1990Co-Authors: Oliver Wiedow, Jensmichael Schroder, Harry Gregory, Janice Young, Enno ChristophersAbstract:Abstract A potent inhibitor of human leukocyte Elastase (EC 3.4.21.37) and porcine pancreatic Elastase (EC 3.4.21.36) was purified to homogeneity from human horny layers. It inhibits human leukocyte Elastase and porcine pancreatic Elastase in a 1:1 molar ratio and shows equilibrium dissociation constants of 6 x 10(-10) M and 1 x 10(-9) M, respectively. Inhibition of plasmin, trypsin, alpha-chymotrypsin, and cathepsin G was not observed. This inhibitor proved to be an acid stable basic peptide with an isoelectric point of 9.7. The complete amino acid sequence appears to be unique with 38% homology to the C-terminal half of antileukoprotease. The sequence shows that the inhibitor is composed of 57 amino acids and predicts a Mr of 7017. The high affinity as well as the apparent specificity for Elastases suggests a functional role in preventing Elastase-mediated tissue proteolysis. It is suggested that the term "elafin" be used to designate this inhibitor.
Jianhong Li - One of the best experts on this subject based on the ideXlab platform.
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a spider araneus ventricosus chymotrypsin inhibitor that acts as an Elastase inhibitor and a microbial serine protease inhibitor
Comparative Biochemistry and Physiology B, 2013Co-Authors: Miao Yuan, Sha Zhan, Jianhong LiAbstract:Spider-derived Kunitz-type serine protease inhibitors have been shown to exhibit plasmin and Elastase inhibition activity and potassium channel blocking activity, but thus far, no additional roles for spider-derived chymotrypsin inhibitors have been elucidated. In this study, a spider (Araneus ventricosus) chymotrypsin inhibitor (AvCI) that acts as an Elastase inhibitor and a microbial serine protease inhibitor was identified. AvCI is a 70-amino acid mature peptide that displays eight conserved cysteine residues and a P1 lysine residue. Recombinant AvCI expressed in baculovirus-infected insect cells demonstrated inhibitory activity against chymotrypsin (Ki 49.85 nM), but not trypsin, which defines a role for AvCI as a spider-derived chymotrypsin inhibitor. AvCI also exhibited inhibitory activity against microbial serine proteases such as subtilisin A (Ki 20.51 nM) and proteinase K (Ki 65.42 nM). Furthermore, AvCI exhibited no detectable inhibitory effects on factor Xa, thrombin, tissue plasminogen activator, or plasmin; however, AvCI strongly inhibited human neutrophil Elastase (Ki 8.74 nM) and porcine pancreatic Elastase (Ki 11.32 nM), indicating that AvCI acts as an anti-elastolytic factor. These findings constitute molecular evidence that AvCI acts as an inhibitor against chymotrypsin, microbial serine proteases, and Elastases. This paper provides a novel view of the functions of a spider-derived chymotrypsin inhibitor.
B Lembcke - One of the best experts on this subject based on the ideXlab platform.
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immunoreactive Elastase i clinical evaluation of a new noninvasive test of pancreatic function
Clinical Chemistry, 1996Co-Authors: Jurgen Stein, Michael Jung, A Sziegoleit, S Zeuzem, W F Caspary, B LembckeAbstract:We have evaluated the diagnostic value of the fecal Elastase test in comparison with the secretin-pancreozymin test in the diagnosis of exocrine pancreatic insufficiency. Pancreatic Elastase was measured immunologically. Immunoreactive Elastase activity in spot stools from controls ranged from 136 to 4440 microgram/g; 95% of all values were within 175 to 1500 microgram/g. The Elastase assay CVs ranged from 3.3% to 6.3% (intraassay) and from 4.1% to 10.2% (interassay). The output of Elastase correlated well with those of amylase, lipase, and trypsin, yielding respective correlation coefficients of 0.83, 0.82, and 0.84 in controls and 0.86, 0.91, and 0.91 in patients with impaired pancreatic function. In contrast to fecal chymotrypsin, the test results were unaffected by pancreatic enzyme replacement therapy. These results indicate that fecal immunoreactive Elastase may be recommended as a new, noninvasive tubeless test of pancreatic function.
Nigel W Bunnett - One of the best experts on this subject based on the ideXlab platform.
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neutrophil Elastase activates protease activated receptor 2 par2 and transient receptor potential vanilloid 4 trpv4 to cause inflammation and pain
Journal of Biological Chemistry, 2015Co-Authors: Peishen Zhao, Tinamarie Lieu, Nicholas Barlow, Silvia Sostegni, Silke Haerteis, Christoph Korbmacher, Wolfgang Liedtke, Nestor N Jimenezvargas, Stephen Vanner, Nigel W BunnettAbstract:Proteases that cleave protease-activated receptor-2 (PAR2) at Arg36↓Ser37 reveal a tethered ligand that binds to the cleaved receptor. PAR2 activates transient receptor potential (TRP) channels of nociceptive neurons to induce neurogenic inflammation and pain. Although proteases that cleave PAR2 at non-canonical sites can trigger distinct signaling cascades, the functional importance of the PAR2-biased agonism is uncertain. We investigated whether neutrophil Elastase, a biased agonist of PAR2, causes inflammation and pain by activating PAR2 and TRP vanilloid 4 (TRPV4). Elastase cleaved human PAR2 at Ala66↓Ser67 and Ser67↓Val68. Elastase stimulated PAR2-dependent cAMP accumulation and ERK1/2 activation, but not Ca2+ mobilization, in KNRK cells. Elastase induced PAR2 coupling to Gαs but not Gαq in HEK293 cells. Although Elastase did not promote recruitment of G protein-coupled receptor kinase-2 (GRK2) or β-arrestin to PAR2, consistent with its inability to promote receptor endocytosis, Elastase did stimulate GRK6 recruitment. Elastase caused PAR2-dependent sensitization of TRPV4 currents in Xenopus laevis oocytes by adenylyl cyclase- and protein kinase A (PKA)-dependent mechanisms. Elastase stimulated PAR2-dependent cAMP formation and ERK1/2 phosphorylation, and a PAR2- and TRPV4-mediated influx of extracellular Ca2+ in mouse nociceptors. Adenylyl cyclase and PKA-mediated Elastase-induced activation of TRPV4 and hyperexcitability of nociceptors. Intraplantar injection of Elastase to mice caused edema and mechanical hyperalgesia by PAR2- and TRPV4-mediated mechanisms. Thus, the Elastase-biased agonism of PAR2 causes Gαs-dependent activation of adenylyl cyclase and PKA, which activates TRPV4 and sensitizes nociceptors to cause inflammation and pain. Our results identify a novel mechanism of Elastase-induced activation of TRPV4 and expand the role of PAR2 as a mediator of protease-driven inflammation and pain.