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Serine Proteinase Inhibitors (serine + proteinase_inhibitor)
Selected AbstractsIdentification of membrane-bound serine proteinase matriptase as processing enzyme of insulin-like growth factor binding protein-related protein-1 (IGFBP-rP1/angiomodulin/mac25)FEBS JOURNAL, Issue 3 2006Sanjida Ahmed Insulin-like growth factor (IGF) binding protein-related protein-1 (IGFBP-rP1) modulates cellular adhesion and growth in an IGF/insulin-dependent or independent manner. It also shows tumor-suppressive activity in vivo. We recently found that a single-chain IGFB-rP1 is proteolytically cleaved to a two-chain form by a trypsin-like, endogenous serine proteinase, changing its biological activities. In this study, we attempted to identify the IGFBP-rP1-processing enzyme. Of nine human cell lines tested, seven cell lines secreted IGFBP-rP1 at high levels, and two of them, ovarian clear cell adenocarcinoma (OVISE) and gastric carcinoma (MKN-45), highly produced the cleaved IGFBP-rP1. Serine proteinase inhibitors effectively blocked the IGFBP-rP1 cleavage in the OVISE cell culture. The conditioned medium of OVISE cells did not cleave purified IGFBP-rP1, but their membrane fraction had an IGFBP-rP1-cleaving activity. The membrane fraction contained an 80-kDa gelatinolytic enzyme, which was identified as the membrane-type serine proteinase matriptase (MT-SP1) by immunoblotting. When the membrane fraction was separated by SDS/PAGE, the IGFBP-rP1-cleaving activity comigrated with matriptase. A soluble form of matriptase purified in an inhibitor-free form efficiently cleaved IGFBP-rP1 at the same site as that found in a naturally cleaved IGFBP-rP1. Furthermore, small interfering RNAs for matriptase efficiently blocked both the matriptase expression and the cleavage of IGBP-rP1 in OVISE cells. These results demonstrate that IGFBP-rP1 is processed to the two-chain form by matriptase on the cell surface. [source] IDENTIFICATION OF A MYOFIBRIL-BOUND SERINE PROTEINASE IN THE SKELETAL MUSCLE OF SILVER CARPJOURNAL OF FOOD BIOCHEMISTRY, Issue 5 2004MIN-JIE CAO ABSTRACT Myofibril-bound serine proteinase (MBSP) in the skeletal muscle of silver carp was characterized. Myosin heavy chain (MHC) degraded markedly when silver carp myofibril was incubated at 55,60C as shown by SDS-PAGE. Prolonged incubation of myofibrils also caused the degradation of other myofibrillar proteins such as ,-actinin, actin and tropomyosin to some degree. The results suggest the existence of an endogenous myofibril associated proteinase. Serine proteinase inhibitors (Pefabloc SC and Lima bean trypsin inhibitor) greatly suppressed the degradation of myosin heavy chain, while inhibitors for cysteine, metallo, and aspartic proteinases did not show any effect, indicating that the endogeneous proteinase is a myofibril-bound serine proteinase. [source] Neutrophil elastase in pressure ulcer fluid degrades fibronectin in the exudatesGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 3 2004Shingo Ai Background: Pressure ulcers are classified as chronic wounds, which do not heal in a timely fashion. Fibronectin is condensed in granulation tissue, and essential glycoprotein of wound healing. It has been proposed that fibronectin degradation may be involved in delaying wound healing. We have investigated whether pressure ulcer fluid (PUF) contains degraded fibronectin. In addition, we tried to identify the proteinase which contributes to fibronectin degradation in PUF. Methods: Fibronectin degradation and the presence of neutrophil elastase (NE) in PUF were determined by immunoblot analysis. Fibronectin degradation activity in PUF was determined in the presence of various proteinase inhibitors. NE activity was assessed using NE specific substrate. Results: Immunoblot analysis revealed that degraded fibronectin was observed in PUF samples but not in acute wound fluid (AWF). The PUF contained a proteinase capable of degrading freshly added fibronectin and its activity in PUF was blocked by a broad-spectrum serine proteinase inhibitor or sivelestat, a specific neutrophil elastase inhibitor, but not by metalloproteinase and cysteine proteinase inhibitors. Immunoblot analysis of PUF using an antineutrophil elastase antibody revealed that neutrophil elastase was detected as three bands at molecular weights of ,30 kDa, ,38 kDa, and ,54 kDa, indicating that neutrophil elastase in the exudates existed not only as free monomers, but also in polymers or complexes with other molecules. Conclusion: These results suggest that PUF contains a high level of neutrophil elastase which may be involved in the delay of the healing of pressure ulcer through the fibronectin degradation. [source] Expression analysis of genes induced in barley after chemical activation reveals distinct disease resistance pathwaysMOLECULAR PLANT PATHOLOGY, Issue 5 2000Katrin Beßer Salicylic acid (SA) and its synthetic mimics 2,6-dichloroisonicotinic acid (DCINA) and benzo(1,2,3)thiadiazole-7-carbothioic acid S-methyl ester (BTH), protect barley systemically against powdery mildew (Blumeria graminis f.sp. hordei, Bgh) infection by strengthening plant defence mechanisms that result in effective papillae and host cell death. Here, we describe the differential expression of a number of newly identified barley chemically induced (BCI) genes encoding a lipoxygenase (BCI-1), a thionin (BCI-2), an acid phosphatase (BCI-3), a Ca2+ -binding EF-hand protein (BCI-4), a serine proteinase inhibitor (BCI-7), a fatty acid desaturase (BCI-8) and several further proteins with as yet unknown function. Compared with SA, the chemicals DCINA and BTH were more potent inducers of both gene expression and resistance. Homologues of four BCI genes were detected in wheat and were also differentially regulated upon chemical activation of disease resistance. Except for BCI-4 and BCI-5 (unknown function), the genes were also induced by exogenous application of jasmonates, whereas treatments that raise endogenous jasmonates as well as wounding were less effective. The fact that BCI genes were not expressed during incompatible barley,Bgh interactions governed by gene-for-gene relationships suggests the presence of separate pathways leading to powdery mildew resistance. [source] REVIEW ARTICLE: Evolution and Function of the Uterine Serpins (SERPINA14)AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010Maria B. Padua Citation Padua MB, Hansen PJ. Evolution and function of the uterine serpins (SERPINA14). Am J Reprod Immunol 2010 Uterine serpins (recently designated as SERPINA14) are hormonally induced proteins secreted in large quantities by the endometrial epithelium during pregnancy. The SERPINA14 proteins belong to the serine proteinase inhibitor (serpin) superfamily, but their apparent lack of inhibitory activity toward serine proteinases suggests that these proteins evolved a different function from the anti-proteinase activity typically found in most members of the serpin superfamily. The gene is present in a limited group of mammals in the Laurasiatheria superorder (ruminants, horses, pigs, dolphins and some carnivores) while being absent in primates, rodents, lagomorphs and marsupials. Thus, the gene is likely to have evolved by gene duplication after divergence of Laurasiatheria and to play an important role in pregnancy. That role may vary between species. In sheep, SERPINA14 probably serves an immunoregulatory role to prevent rejection of the fetal allograft. It is inhibitory to lymphocyte proliferation and natural killer cell function. In the pig, SERPINA14 is involved in iron transport to the fetus by binding to and stabilizing the iron-binding protein uteroferrin. It is possible that SERPINA14 has undergone divergence in function since the original emergence of the gene in a common ancestor of species possessing SERPINA14. [source] Momordica charantia trypsin inhibitor II inhibits growth and development of Helicoverpa armigeraINSECT SCIENCE, Issue 5 2009Manasi Alok Telang Abstract, Bitter gourd (Momordica charantia L.) seeds contain several squash-type serine proteinase inhibitors (PIs), which inhibit the digestive proteinases of the polyphagous insect pest Helicoverpa armigera. In the present work isolation of a DNA sequence encoding the mature peptide of a trypsin inhibitor McTI-II, its cloning and expression as a recombinant protein using Pichia pastoris have been reported. Recombinant McTI-II inhibited bovine trypsin at 1: 1 molar ratio, as expected, but did not inhibit chymotrypsin or elastase. McTI-II also strongly inhibited trypsin-like proteinases (81% inhibition) as well as the total proteolytic activity of digestive proteinases (70% inhibition) from the midgut of H. armigera larvae. The insect larvae fed with McTI-II-incorporated artificial diet suffered over 70% reduction in the average larval weight after 12 days of feeding. Moreover, ingestion of McTI-II resulted in 23% mortality in the larval population. The strong antimetabolic activity of McTI-II toward H. armigera indicates its probable use in developing insect tolerance in susceptible plants. [source] Emerging multifunctional aspects of cellular serine proteinase inhibitors in tumor progression and tissue regenerationPATHOLOGY INTERNATIONAL, Issue 2 2002Hiroaki Kataoka First page of article [source] Topography of a 2.0 Å structure of ,1 -antitrypsin reveals targets for rational drug design to prevent conformational diseasePROTEIN SCIENCE, Issue 7 2000Peter R. Elliott Abstract Members of the serpin family of serine proteinase inhibitors play important roles in the inflammatory, coagulation, fibrinolytic, and complement cascades. An inherent part of their function is the ability to undergo a structural rearrangement, the stressed (S) to relaxed (R) transition, in which an extra strand is inserted into the central A ,-sheet. In order for this transition to take place, the A sheet has to be unusually flexible. Malfunctions in this flexibility can lead to aberrant protein linkage, serpin inactivation, and diseases as diverse as cirrhosis, thrombosis, angioedema, emphysema, and dementia. The development of agents that control this conformational rearrangement requires a high resolution structure of an active serpin. We present here the topology of the archetypal serpin ,1 -antitrypsin to 2 Å resolution. This structure allows us to define five cavities that are potential targets for rational drug design to develop agents that will prevent conformational transitions and ameliorate the associated disease. [source] Immunoregulatory Activity, Biochemistry, and Phylogeny of Ovine Uterine SerpinAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2001MORGAN R. PELTIER PROBLEM: During pregnancy, the endometrium of the ewe secretes a progesterone-induced member of the serpin superfamily of serine proteinase inhibitors called ovine uterine serpin (OvUS) that has immunosuppressive properties. METHOD: Review of the literature. RESULTS AND CONCLUSIONS: OvUS inhibits a wide variety of immune responses, including mixed lymphocyte reaction, mitogen-stimulated lymphocyte proliferation, and T cell-dependent antibody production. Recent data have suggested that OvUS functions by inhibiting protein kinase C and interleukin-2-mediated events. OvUS and similar genes present in cattle and pigs diverged from other serpins prior to the divergence of artiodactyls. Since this time, the serpins have apparently undergone adaptive evolution that has led to a conformational state and biological functions distinct from prototypical serpins. Thus, it is likely that these proteins have an important role in the reproductive biology of Artiodactyla. Several lines of evidence suggest that, in sheep, OvUS functions to mediate the immunosuppressive effects of progesterone and prevent immunological rejection of the fetal allograft. [source] | ||||||||||||||||