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serin protease inhibitor

Jia-Hui Gao, Meng-Ya Zeng, Xiao-Hua Yu, Gao-Feng Zeng, Lin-Hao He, Xi-Long Zheng, Da-Wei Zhang, Xin-Ping Ouyang, Chao-Ke Tang
Atherosclerosis is a dyslipidemia disease characterized by foam cell formation driven by the accumulation of lipids. Visceral adipose tissue-derived serine protease inhibitor (vaspin) is known to suppress the development of atherosclerosis via its anti-inflammatory properties, but it is not yet known whether vaspin affects cholesterol efflux in THP-1 macrophage-derived foam cells. Here, we investigated the effects of vaspin on ABCA1 expression and cholesterol efflux, and further explored the underlying mechanism...
April 10, 2018: Biochemical and Biophysical Research Communications
Ying Zhang, Jin Guo, Li He, Hong-Ying Zong, Guo-Bin Cai
Serine proteinase inhibitor (Serpin, SPI) is a vital superfamily of endogenous inhibitors that monitor proteolytic events active in a number of biological functions. In this study, we isolated a full length gene encoding a novel serine protease inhibitor of Schistosoma japonicum (SjSPI) and characterized its molecular properties. Our result showed that SjSPI contained an open reading frame of 1,218 bp, which encoded 405 amino acid residues. Chromosomal structure analysis showed that SjSPI gene was comprised of six exons separated by five introns...
April 9, 2018: Parasitology International
Ronak Tilvawala, Son Hong Nguyen, Aaron J Maurais, Venkatesh V Nemmara, Mitesh Nagar, Ari J Salinger, Sunil Nagpal, Eranthie Weerapana, Paul R Thompson
Increased protein citrullination is linked to various diseases including rheumatoid arthritis (RA), lupus, and cancer. Citrullinated autoantigens, a hallmark of RA, are recognized by anti-citrullinated protein antibodies (ACPAs) which are used to diagnose RA. ACPA-recognizing citrullinated enolase, vimentin, keratin, and filaggrin are also pathogenic. Here, we used a chemoproteomic approach to define the RA-associated citrullinome. The identified proteins include numerous serine protease inhibitors (Serpins), proteases and metabolic enzymes...
March 21, 2018: Cell Chemical Biology
Qiuyu Fan, Hong Li, Yingfen Qin, Li Li, Lulin Chen, Lulu Zhang, Yingnan Lv, Danyan Liang, Yaojie Liang, Tianzhu Long, Lianguang Xie, Haisheng Yang, Chunting Dong, Haiying Zhang
BACKGROUND: Plasminogen activator inhibitor-1 (PAI-I), encoded by SERPINE1 gene, is a member of the serine protease inhibitor superfamily, and polymorphisms in SERPINE1 have been reported to be associated with type 2 diabetes (T2D). This study investigated whether the polymorphism in PAI-I contribute to the risk for T2D. METHODS: A 1:1 case-control study was conducted to investigate the association of rs6092 in SERPINE1 with T2D and diabetes-related metabolic traits, including body mass index, waist circumference (WC), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol, low density lipoprotein cholesterol, fasting plasma glucose and glycosylated hemoglobin (HbA1c) in a Chinese population, with a total of 1572 subjects (786 T2D patients and 786 healthy controls)...
April 5, 2018: Gene
Danielle M Dunlea, Laura T Fee, Thomas McEnery, Noel G McElvaney, Emer P Reeves
Alpha-1 antitrypsin (AAT) is the most abundant serine protease inhibitor circulating in the blood. AAT deficiency (AATD) is an autosomal codominant condition affecting an estimated 3.4 million individuals worldwide. The clinical disease associated with AATD can present in a number of ways including COPD, liver disease, panniculitis and antineutrophil cytoplasmic antibody vasculitis. AATD is the only proven genetic risk factor for the development of COPD, and deficient individuals who smoke are disposed to more aggressive disease...
2018: Journal of Inflammation Research
Roman Szabo, Thomas H Bugge
Prostasin (CAP1/PRSS8) is a glycosylphosphatidylinositol (GPI)-anchored serine protease that is essential for epithelial development and overall survival in mice. Prostasin is regulated primarily by the transmembrane serine protease inhibitor, hepatocyte growth factor activator inhibitor (HAI)-2, and loss of HAI-2 function leads to early embryonic lethality in mice due to an unregulated prostasin activity. We have recently reported that critical in vivo functions of prostasin can be performed by proteolytically-inactive or zymogen-locked variants of the protease...
2018: PloS One
Anastasia Chillà, Francesca Margheri, Alessio Biagioni, Mario Del Rosso, Gabriella Fibbi, Anna Laurenzana
BACKGROUND: Controlling vascular growth is a challenging aim for the inhibition of tumor growth and metastasis. The amoeboid and mesenchymal types of invasiveness are two modes of migration interchangeable in cancer cells: the Rac-dependent mesenchymal migration requires the activity of proteases; the Rho-ROCK-dependent amoeboid motility is protease-independent and has never been described in endothelial cells. METHODS: A cocktail of physiologic inhibitors (Ph-C) of serine-proteases, metallo-proteases and cysteine-proteases, mimicking the physiological environment that cells encounter during their migration within the angiogenesis sites was used to induce amoeboid style migration of Endothelial colony forming cells (ECFCs) and mature endothelial cells (ECs)...
April 3, 2018: Journal of Experimental & Clinical Cancer Research: CR
Yosuke Masuda, Tomoki Yoshida, Noriyuki Yamaotsu, Shuichi Hirono
We recently reported that the Gibbs free energy of hydrolytic water molecules (ΔGwat ) in acyl-trypsin intermediates calculated by hydration thermodynamics analysis could be a useful metric for estimating the catalytic rate constants (kcat ) of mechanism-based reversible covalent inhibitors. For thorough evaluation, the proposed method was tested with an increased number of covalent ligands that have no corresponding crystal structures. After modeling acyl-trypsin intermediate structures using flexible molecular superposition, ΔGwat values were calculated according to the proposed method...
2018: Chemical & Pharmaceutical Bulletin
Mel Berger, Mingyao Liu, Marc E Uknis, Maria Koulmanda
Limited availability of donor organs and risk of ischemia-reperfusion injury (IRI) seriously restrict organ transplantation. Therapeutics that can prevent or reduce IRI could potentially increase the number of transplants by increasing use of borderline organs and decreasing discards. Alpha-1 antitrypsin (AAT) is an acute phase reactant and serine protease inhibitor which limits inflammatory tissue damage. Purified plasma-derived AAT has been well-tolerated in more than 30 years of use to prevent emphysema in AAT deficient individuals...
April 1, 2018: American Journal of Transplantation
Paulo C Maffía, Diego Guerrieri, Ximena Villalonga, Fiorella Caro, Sonia Gómez, Nancy Tateosian, Betiana P Bogado, Mercedes L Sánchez, Nella Ambrosi, Eduardo Chuluyan
Secretory Leukocyte Proteinase Inhibitor (SLPI) is an antiinflammatory peptide that blocks the activity of serine proteases, primarily the neutrophil elastase. In an attempt to direct the activity of SLPI on inflamed sites, a chimera consisting of the transglutaminase II substrate domain of trappin 2 (cementoin), and the mature SLPI protein was constructed. Cell attachment and biological activity were compared between SLPI and this chimera. By using whole cell ELISA, fluorescence microscopy and flow cytometry assays we observed that the cementoin-SLPI fusion protein (FP) but not SLPI attached to a human lung epithelial cell line and monocytes...
March 28, 2018: Scientific Reports
Mariko Yamada, Hideki Hayashi, Moe Yuuki, Nahoko Matsushima, Bo Yuan, Norio Takagi
The proprotein convertases (PCs) act as serine proteases and are known to convert diverse precursor proteins into their active forms. Among the PCs, furin has been considered to play a crucial role not only in embryogenesis, but also in the initiation and progression of certain pathologic conditions. However, the roles played by furin with respect to neuronal cell injuries remain to be determined. An excessive influx of Ca2+ through the N-methyl-d-aspartate (NMDA) receptor has been associated with diverse neurological and neurodegenerative disorders...
March 26, 2018: Scientific Reports
Kristin E Hirabayashi, Anthony T Moore, Bryce A Mendelsohn, Ryan J Taft, Aditi Chawla, Denise Perry, Duncan Henry, Anne Slavotinek
Congenital sodium diarrhea is a rare and life-threatening disorder characterized by a severe, secretory diarrhea containing high concentrations of sodium, leading to hyponatremia and metabolic acidosis. It may occur in isolation or in association with systemic features such as facial dysmorphism, choanal atresia, imperforate anus, and corneal erosions. Mutations in the serine protease inhibitor, Kunitz-Type 2 (SPINT2) gene have been associated with congenital sodium diarrhea and additional syndromic features...
April 2018: American Journal of Medical Genetics. Part A
Kimberly Stephens, Richard A Cardullo, Catherine D Thaler
In most animals, sperm are stored in a quiescent state in the male reproductive tract and only initiate motility when released into either the female reproductive tract, or, in the case of broadcast spawners, the external environment. Male accessory gland secretions transferred into the female reproductive tract may provide factors that modulate sperm viability and storage, or aid in sperm competition, as well as activate sperm motility. In several insects, serine proteases have been implicated in activating sperm motility...
March 24, 2018: Molecular Reproduction and Development
Rishi Kumar Jaiswal, Akhil Kumar Varshney, Pramod Kumar Yadava
The urokinase plasminogen activator system is a family of serine proteases which consists of uPA (urokinase plasminogen activator), uPAR (urokinase type plasminogen activator receptor) and PAI-1 (plasminogen activator inhibitor 1). In addition to their significant roles in activation, these proteases act as key regulators of the tumor microenvironment and are involved in the metastatic process in many cancers. High levels of uPA system proteases in many human cancer predicts poor patient prognosis and strongly indicated a key role of uPA system in cancer metastasis...
February 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Md Shamimuzzaman, Lila Vodkin
To understand translational capacity on a genome-wide scale across three developmental stages of immature soybean seed cotyledons, ribosome profiling was performed in combination with RNA sequencing and cluster analysis. Transcripts representing 216 unique genes demonstrated a higher level of translational activity in at least one stage by exhibiting higher translational efficiencies (TEs) in which there were relatively more ribosome footprint sequence reads mapping to the transcript than were present in the control total RNA sample...
2018: PloS One
Ying Yang, Xiangke Xin, Xing Fu, Danmei Xu
Serine proteinase inhibitor, clade E member 2 ( SERPINE2 ), also known as protease nexin-1 (PN-1), is a member of the serpin family. Despite several reported roles of SERPINE2 in tumor development the histological distribution of SERPINE2 and its expression levels in a large variety of tumors remains unclear. Through expressed sequence tag database analysis, immunohistochemical staining of tissue microarrays and a literature review, it was revealed that SERPINE2 expression varied according to growth stages and tissue types...
April 2018: Oncology Letters
Amjad M Husaini, Kyoko Morimoto, Balakumaran Chandrasekar, Steven Kelly, Farnusch Kaschani, Daniel Palmero, Jianbing Jiang, Markus Kaiser, Oussama Ahrazem, Hermen S Overkleeft, Renier A L van der Hoorn
With nearly 140 α-glycosidases in 14 different families, plants are well equipped with enzymes that can break the α-glucosidic bonds in a large diversity of molecules. Here, we introduce activity-based protein profiling (ABPP) of α-glycosidases in plants using α-configured cyclophellitol aziridine probes carrying various fluorophores or biotin. In Arabidopsis (Arabidopsis thaliana), these probes label members of the GH31 family of Glycosyl Hydrolases, including ER-resident α-glucosidase-II RSW3/PSL5 (Radial Swelling-3/Priority for Sweet Life-5) and Golgi-resident α-mannosidase-II HGL1, both of which trim N-glycans on glycoproteins...
March 19, 2018: Plant Physiology
Aleksandra Losvik, Lisa Beste, Jennifer Stephens, Lisbeth Jonsson
Aphids are serious pests in crop plants. In an effort to identify plant genes controlling resistance against aphids, we have here studied a protease inhibitor, CI2c in barley (Hordeum vulgare L.). The CI2c gene was earlier shown to be upregulated by herbivory of the bird cherry-oat aphid (Rhopalosiphum padi L.) in barley genotypes with moderate resistance against this aphid, but not in susceptible lines. We hypothesized that CI2c contributes to the resistance. To test this idea, cDNA encoding CI2c was overexpressed in barley and bioassays were carried out with R...
2018: PloS One
Yongjie Liu, Fujun Hou, Zhaoying Qian, Xiaolin Liu
The clade B serpins contain predominantly intracellular proteins and were reported to be involved in multiple biological functions, especially in inflammation and immune system function. However, studies about the role of the invertebrate intracellular serpins in immune responses were still deficient. Therefore, this paper focused on the functional characterization of LvserpinB3 in white shrimp Litopenaeus vannamei. The pAc5.1-LvserpinB3-EGFP vector was transfected into Drosophila Schneider 2 (S2) cells to analyze the subcellular localization of LvserpinB3, and fluorescent imaging showed that LvserpinB3 were mainly localized to the mitochondria...
March 14, 2018: Developmental and Comparative Immunology
Koji Yamamoto, Makiko Kawaguchi, Takeshi Shimomura, Aya Izumi, Kazuomi Konari, Arata Honda, Chen-Yong Lin, Michael D Johnson, Yoshihiro Yamashita, Tsuyoshi Fukushima, Hiroaki Kataoka
Hepatocyte growth factor activator inhibitor (HAI)-1/ SPINT1 and HAI-2/ SPINT2 are membrane-anchored protease inhibitors having homologous Kunitz-type inhibitor domains. They regulate membrane-anchored serine proteases, such as matriptase and prostasin. Whereas HAI-1 suppresses the neoplastic progression of keratinocytes to invasive squamous cell carcinoma (SCC) through matriptase inhibition, the role of HAI-2 in keratinocytes is poorly understood. In vitro homozygous knockout of the SPINT2 gene suppressed the proliferation of two oral SCC (OSCC) lines (SAS and HSC3) but not the growth of a non-tumorigenic keratinocyte line (HaCaT)...
February 20, 2018: Oncotarget
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