China
Africa
Explore chapters and articles related to this topic
Reduction and Fixation of Sacroiliac joint Dislocation by the Combined Use of S1 Pedicle Screws and an Iliac Rod
Published in Kai-Uwe Lewandrowski, Donald L. Wise, Debra J. Trantolo, Michael J. Yaszemski, Augustus A. White, Advances in Spinal Fusion, 2003
Kai-Uwe Lewandrowski, Donald L. Wise, Debra J. Trantolo, Michael J. Yaszemski, Augustus A. White
TGF- β1 is the proteotypic member of the TGF β1superfamily consisting of activins, inhib-ins, mullerian-inhibiting substance, other TGF- β1 and bone morphogenetic proteins (BMPs). This family of over 40 related growth and differentiation factors has gained many new members since the discovery of TGF- βl (Fig. 6) [11]. TGF- β1 is synthesized as part of a larger inactive protein consisting of two disulfide linked, cy steine-rich 12-15 kDa polypeptides. Furin proteases activate this precursor molecule through enzymatic cleavage and release of the biologically active C-terminal region [12]. It is this active protein that serves as a potent osteoactive factor.
Introduction to Bioresponsive Polymers
Published in Deepa H. Patel, Bioresponsive Polymers, 2020
Deepa H. Patel, Drashti Pathak, Neelang Trivedi
A member of the pro-protein convertase family, furin has a key role in tumor development, metastasis, and angiogenesis. In one investigation, a furin-cleavable peptide cross-linker was fused with drug-delivery carriers, which could be degraded gradually to release payload protein along their cellular uptake pathway [44]. In a recent investigation, a graphene-based co-delivery system took benefit of the trans-membrane activity of furin to cleave the furin-degradable substrate for the exposure of TRAIL in the direction of the membrane [45].
FRET Reporter Molecules for Identification of Enzyme Functions
Published in Grunwald Peter, Biocatalysis and Nanotechnology, 2017
Jing Mu, Hao Lun Cheong, Bengang Xing
Proprotein convertases are the subfamily of subtilases, which belongs to the family of subtilisin-like serine proteases. These convertases associate with the activation of cellular and pathogenic precursor proteins like polypeptide hormones, growth factors and bacterial pathogens, etc. They consist of nine family members: convertase 1 (PC1), PC2, furin, PC4, PC5, paired basic amino acid cleaving enzyme 4 (PACE4), PC7, subtilisin kexin isozyme 1 (SKI-1) and proprotein convertase subtilisin kexin 9 (PCSK9) (Seidah et al., 2012). Currently, proprotein convertases are considered to be attractive targets due to their important functions in the progression of various diseases such as cancer, inflammation and pathogenic infections (Seidah et al., 2012). Recently, Mu et al. (2014) utilized a small molecule based FRET reporter to realtime monitor furin activities (Fig. 13.15). They designed the probe by using furin recognizable cleaving peptide sequence (RVRRSVK) as the framework for their probe. Using a FRET pair fluorescein (FITC) and quencher 4-(dimethylaminoazo)benzene- 4-carboxamide (Dabcyl) in the probe, they were able to observe a “turn-on” fluorescence effect upon furin cleavage. In addition, the lipid membrane anchor was designed to effectively immobilize the unique reporter onto the cell surface. Using this system, they tested it on various furin positive and negative cells lines. It was observed that the probe was selective to furin expressed cell lines. Furthermore, the probe was capable of staining the cell membrane for relatively quite long time (up to 2 h). In addition, they used the probe in two-photon imaging to prove the utility of the probe in monitoring living cells or tissues. The successful mouse’s ear tissues imaging proved the potential of the probe in monitoring furin activities in vivo and clinic trials.
High-level production and purification of bioactive recombinant human activin A in Chinese hamster ovary cells
Published in Preparative Biochemistry & Biotechnology, 2023
Changin Kim, Hyunjoo Kim, Jeong Soo Park, Jiwon Park, Jeongmin Oh, Jaeseung Yoon, Kwanghee Baek
Activins, disulfide-linked homo- and heterodimers of inhibin β subunits and member of the transforming growth factor-β (TGF-β) superfamily, were originally recognized for their capacity to induce the release of follicle-stimulating hormone (FSH).[1,2] Activin A is also a homodimer of the inhibin βΑ subunit which is one of five types of inhibin subunits described so far and is the best characterized.[3,4] Like all members of the TGF-β superfamily, activin A is initially synthesized as a large precursor polypeptide consisting of a secretory signal peptide, pro-domain, and small mature domain. During the processes that occur within the secretory pathway, the formation of a dimer by two precursor subunits occurs by way of the disulfide linkage of conserved cysteine residues located in the mature domains with recognition and cleavage of the polybasic RRRRR motif between pro- and mature domains by furin-like protease releasing a mature form of bioactive activin A.[5,6] Studies on mutagenesis of the cleavage site have suggested that the biological activity of activin A requires proteolytic cleavage between pro- and mature domains.[7] Although activin A contains one glycosylation site in its pro-domain, its biological activity and secretion are unaffected by glycosylation-deficient cases.[8]
Genetic variants affecting chemical mediated skin immunotoxicity
Published in Journal of Toxicology and Environmental Health, Part B, 2022
Isisdoris Rodrigues de Souza, Patrícia Savio de Araujo-Souza, Daniela Morais Leme
The lack of functional LEKTI expression also results in altered proFLG processing (Descargues et al. 2005), which is the major contributor to epidermal barrier function (Fortugno et al. 2012). This occurs because a complex network of serine proteases such as furin, profilaggrin endopeptidase-1 (PEP1), and other proteolytic enzymes and KLKs, act in concert to mediate the multistep cleavage of the FLG precursor (Fortugno et al. 2012), and their activities are influenced by LEKTI functionality. In addition, LEKTI might diminish allergenicity since many allergens are also serine proteinases inhibited by LEKTI proteinase activity (Walley et al. 2001). In this way, mutations in the SPINK5 gene may result in LEKTI proteins unable to control serine peptidase activity, leading to dysfunctional skin barrier and higher TEWL and inflammatory-type reactions (Ramesh et al. 2020) (Table 4).
Agrochemical-mediated cardiotoxicity in zebrafish embryos/larvae: What we do and where we go
Published in Critical Reviews in Environmental Science and Technology, 2023
Yang Yang, Yue Tao, Zixu Li, Yunhe Cui, Jinzhu Zhang, Ying Zhang
At the cardiac developmental level, endocardium-specific expression of Notch signaling regulates cardiac morphogenesis by interacting with multiple signals from the myocardium and epicardium. Disturbances in normal Notch signaling expression induce congenital heart disease and cardiomyopathy (Guillermo et al., 2016; Niessen & Karsan, 2008). In contrast to in humans, Notch receptors and ligands are more abundant in zebrafish but the core activation mechanisms and functions of the Notch signaling pathway are highly conserved across species (Masek & Andersson, 2017). Unlike in the general signaling pathway, both the receptor and ligand of the Notch signaling pathway are membrane proteins, which function as contact points between two cells. When the Notch signaling pathway is activated, the Notch receptor is cleaved three times (1: in the cytoplasm, furin protease in the Golgi apparatus converts Notch protein single-chain precursors into heterodimers via calcium-dependent non-covalent bonding by cleaving the s1 site at the extracellular end of the Notch transmembrane region; 2: when the Notch ligand binds to the extracellular domain of a heterodimer translocated to the cell membrane, ADAM metalloproteinase releases part of the extracellular fragment by cleaving the S2 site on the receptor; 3: γ-secretase cleaves the S3 site on the remaining heterodimer adhered to the cell membrane and forms the Notch intracellular domain) and eventually releases this domain, which forms a transcriptional complex with the CSL in the nucleus, thereby activating expression of the relevant genes (Nemir & Pedrazzini, 2008) (Figure 4).