China
Africa
Explore chapters and articles related to this topic
Proteinase Inhibitors: An Overview of their Structure and Possible Function in the Acute Phase
Published in Andrzej Mackiewicz, Irving Kushner, Heinz Baumann, Acute Phase Proteins, 2020
Serpins are extremely sensitive to proteolytic inactivation by proteinases they do not inhibit,16 and it is apparent that proteolytically modified serpins are able to act as cytokines. Thus, proteolytically modified α1-PI was found to be chemotactic for neutrophils94 and able to stimulate its own synthesis in monocytes.95 Neither activity was found in the virgin molecule, although elastase/α1-PI complexes were found to have the same effect on monocytes. The receptor thought to be responsible for the binding of α1-PI/proteinase complexes to monocytes and cultured hepatoma cells96 may not be the same as that responsible for the removal of α1-PI/proteinase from circulation,97 since the former recognizes proteolytically modified serpins98 whereas the latter does not.87 The ability of modified α1-PI to act as a cytokine is interesting, but the possibility that other serpins may act similarly following proteolytic inactivation by proteinases that they do not inhibit is potentially very significant. For example, α1-ACT is inactivated more readily by proteolysis than α1-PI,16 and this is more likely to be of relevance in a physiologic medium, provided that the modified α1-ACT is a cytokine.
Spontaneous (Unexplained) Thrombosis: The Inherited Basis for the Thrombohemorrhagic Balance
Published in E. Nigel Harris, Thomas Exner, Graham R. V. Hughes, Ronald A. Asherson, Phospholipid-Binding Antibodies, 2020
A serine protease inhibitor (serpin) of possible importance in this context besides AT-III, HC II, a2AP, PC AI and PAI has recently been identified (Protease nexin 1 [PN-1]). It forms a stable 1:1 complex with enzymes such as thrombin and t-PA.43-44 A similar cellular serpin, a platelet surface protein, has also been isolated and characterized.45-47 Furthermore, a plasma nexin has been isolated recently, tetranexin, which is a plasminogen binding protein and thus a potential modulator of fibrinolysis.48
Defects in Coagulation Factors Leading to Recurrent Pregnancy Loss
Published in Howard J.A. Carp, Recurrent Pregnancy Loss, 2020
Control of thrombin generation is essential for normal hemostasis and is achieved by the physiological anticoagulants. One such anticoagulant is tissue factor pathway inhibitor (TFPI), an endothelial-associated protein that downregulates the initial phase of coagulation by inhibiting tissue factor-factor VIIa and factor Xa complex [70]. Another anticoagulant is antithrombin, a multifunctional serpin (serine protease inhibitor) that inhibits essentially almost all the active coagulation factors. A recent study [71] analyzed the association of SNPs in TFPI and antithrombin genes with RPL in 117 nonpregnant women with three or more consecutive losses prior to 20 weeks of pregnancy without a previous history of carrying a fetus to viability, and 264 healthy fertile nonpregnant women who had at least two term deliveries and no known pregnancy losses [72]. The results of the study showed that antithrombin 786G > A variant increases the risk for RPL, while TFPI T-287C variant is protective. Further studies are required to confirm these findings.
Serpina3n: Potential drug and challenges, mini review
Published in Journal of Drug Targeting, 2020
Mehwish Saba Aslam, Liudi Yuan
Serpins interact with proteases in two ways, inhibitory pathway and substrate pathway. In inhibitory pathway, serpin irreversbly bind with target protease to impede its function while in substrate pathway, protease blocks the function of structurally unmodified serpin by binding to it [48]. According to well established understanding of inhibitory serine proteases, upon the formation of non-covalent stable Michealis complex and the subsequent cleavage of the peptide bond, the loop is integrated into the protein core giving rise to an additional beta-sheet and transported the tethered enzyme along with it, to the distal end of the serpin. In this way bounded peptidase is distorted leading to its inactivation which fails to complete peptide bond hydrolysis [9]. Serpina3n/SERPINA3 follow inhibitory pathway. Like other inhibitory serpins, Serpina3n/SERPINA3 commonly exist in two distinct conformations, innate meta-stable stressed form and relaxed stable form (after binding with target protease). Thus attain irreversible stable conformation through inhibition by compromising functional integrity [5,33,48,49]. Energy released during this conformational change is used for the distortion of the target protease [21].
Decrease in alpha-1 antiproteinase antitrypsin is observed in primary Sjogren’s syndrome condition
Published in Autoimmunity, 2020
Brij B. Singh, Joyce Ohm, Fredice O. Quenum Zanbede, Pooja Chauhan, Frans G. M. Kroese, Arjan Vissink, Julian L. Ambrus, Bibhuti B. Mishra
We next identified the factors that could explain as why the expression of alpha-1 antiproteinase antitrypsin was decreased in pSS. Epigenetic modifications have been shown to alter gene expression as well as contribute to pSS [34,44,45], thus, we focussed our attention to see if epigenetic modifications are altered in pSS patients. DNA methylation has been long proposed that is responsible for the stable maintenance of gene expression patterns [41,46]. Specifically, DNA methylation establishes a silent chromatin state by collaborating with proteins that modify nucleosomes [43]. Importantly, our results showed that DNA methylation was altered in serpinina1 gene encoding for alpha-1 antiproteinase antitrypsin. DNA methylation is a post-replication modification that is predominantly found in cytosines of the dinucleotide sequence CpG. The extent of DNA methylation changes in an orchestrated way and alterations in DNA methylation has been shown in various disease conditions. In cancer cells, methylation of CpG islands is known to contribute to gene silencing, suggesting that a similar mechanism could also be present in pSS, which needs to be further identified. Here we show that increased methylation in the promoter region of the serpinina1 gene was observed, which could inhibit the expression of alpha-1 antiproteinase antitrypsin protein. This was also specific as no significant decrease in other serpin genes was observed. Similarly, other epigenetic modifications such as histone modifications could also alter gene expression, and future research is needed to show if histone modifications are also altered in pSS.
Combined proteomics and transcriptomics identifies serpin family C member 1 associated protein as a biomarker of endometriosis
Published in Annals of Medicine, 2023
Xiao-yan Li, Xi Wang, Zhi-yue Gu, Ting-ting Sun, Jin-hua Leng, Qi Yu
SERPINC1 belongs to serpin superfamily of serine proteinase inhibitors with special primary structure. Up to now, 34 serpins have been identified and divided into nine clades in human [31]. Serpin family proteins have been study as potential biomarkers and therapeutic drugs in other disease [32]. After treatment with plasminogen activator inhibitor (PAI) 1 for patients with EM, Gómez et al. found a significant change of serpin-1 in patients, which suggested that the serpin family was indeed a potential target for EM treatment through the antithrombin pathway. However, considering that there are many suptypes in serpin family, whose functions are not completely consistent, and others are rarely reported. We can further study other members of serpin family in the future [33].