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Cathepsin

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https://www.readbyqxmd.com/read/28528273/addition-of-thiols-to-the-double-bond-of-dipeptide-c-terminal-dehydroalanine-as-a-source-of-new-inhibitors-of-cathepsin-c
#1
Paweł Lenartowicz, Maciej Makowski, Bartosz Oszywa, Kinga Haremza, Rafał Latajka, Małgorzata Pawełczak, Paweł Kafarski
Addition of thiols to double bond of glycyl-dehydroalanine and phenyl-dehydroalanine esters provided micromolar inhibitors of cathepsin C. The structure-activity studies indicated that dipeptides containing N-terminal phenylalanine exhibit higher affinity towards the enzyme. A series of C-terminal S-substituted cysteines are responsible for varying interaction with S1 binding pocket of cathepsin C. Depending on diastereomer these compounds most likely act as slowly reacting substrates or competitive inhibitors...
May 17, 2017: Biochimie
https://www.readbyqxmd.com/read/28526573/transcriptomic-variation-of-locally-infected-skin-of-epinephelus-coioides-reveals-the-mucosal-immune-mechanism-against-cryptocaryon-irritans
#2
Yazhou Hu, Anxing Li, Yang Xu, Biao Jiang, Geling Lu, Xiaochun Luo
Fish skin is the largest immunologically active mucosal organ, providing first-line defense against external pathogens. However, the skin-associated immune mechanisms of fish are still unclear. Cryptocaryon irritans is an obligate ectoparasitic ciliated protozoan that infects almost all marine fish, and is believed to be an excellent pathogen model to study fish mucosal immunity. In this study, a de novo transcriptome assembly of Epinephelus coioides skin post C. irritans tail-infection was performed for the first time using the Illumina HiSeq™ 2500 system...
May 16, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28526399/evaluation-of-the-effectiveness-of-chronic-antidepressant-drug-treatments-in-the-hippocampal-mitochondria-a-proteomic-study-in-an-animal-model-of-depression
#3
Katarzyna Głombik, Aneta Stachowicz, Ewa Trojan, Rafał Olszanecki, Joanna Ślusarczyk, Maciej Suski, Katarzyna Chamera, Bogusława Budziszewska, Władysław Lasoń, Agnieszka Basta-Kaim
Several lines of evidence indicate that adverse experience in early life may be a triggering factor for disturbances in the brain mitochondrial proteins and lead to the development of depression in adulthood. On the other hand, little is known about the impact of chronic administration of various antidepressant drugs on the brain mitochondria, as a target for the pharmacotherapy of depression. The purpose of our study was to compare the impact of chronic treatment with two antidepressant drugs with different mechanisms of action, a tricyclic antidepressant (TCA), imipramine, and an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class, fluoxetine, on the mitochondria-enriched subproteome profile in the hippocampus of 3-month-old male rats following a prenatal stress procedure (an animal model of depression)...
May 16, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28522343/exogenous-cathepsin-v-protein-protects-human-cardiomyocytes-hcm-from-angiotensin-%C3%A2-induced-hypertrophy
#4
Kun Huang, Lu Gao, Ming Yang, Jiliang Wang, Zheng Wang, Lin Wang, Guobin Wang, Huili Li
Angiotensin (Ang) Ⅱ-induced cardiac hypertrophy can deteriorate to heart failure, a leading cause of mortality. Endogenous Cathepsin V (CTSV) has been reported to be cardioprotective against hypertrophy. However, little is known about the effect of exogenous CTSV on cardiac hypertrophy. We used the human cardiomyocytes HCM as a cell model to investigate the effects of exogenous CTSV on Ang Ⅱ-induced cardiac cell hypertrophy. Cell surface area and expression of classical markers of hypertrophy were analyzed...
May 15, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28517962/inhibition-of-the-continuum-of-radiation-induced-normal-tissue-injury-by-a-redox-active-mn-porphyrin
#5
Samuel R Birer, Chen-Ting Lee, Kingshuk Roy Choudhury, Kenneth H Young, Ivan Spasojevic, Ines Batinic-Haberle, James D Crapo, Mark W Dewhirst, Kathleen A Ashcraft
Normal tissue damage after head and neck radiotherapy involves a continuum of pathologic events to the mucosa, tongue and salivary glands. We examined the radioprotective effects of MnBuOE, a redox-active manganese porphyrin, at three stages of normal tissue damage: immediate (leukocyte endothelial cell [L/E] interactions), early (mucositis) and late (xerostomia and fibrosis) after treatment. In this study, mice received 0 or 9 Gy irradiation to the oral cavity and salivary glands ± MnBuOE treatment. Changes in leukocyte-endothelial cell interactions were measured 24 h postirradiation...
May 18, 2017: Radiation Research
https://www.readbyqxmd.com/read/28513557/calcium-supplement-derived-from-gallus-gallus-domesticus-promotes-bmp-2-runx2-smad5-and-suppresses-trap-rank-expression-through-mapk-signaling-activation
#6
Han Seok Yoo, Gyung-Ji Kim, Da Hye Song, Kang-Hyun Chung, Kwon-Jai Lee, Dong-Hee Kim, Jeung Hee An
The present study evaluated the effects of a calcium (Ca) supplement derived from Gallus gallus domesticus (GD) on breaking force, microarchitecture, osteogenic differentiation and osteoclast differentiation factor expression in vivo in Ca-deficient ovariectomized (OVX) rats. One percent of Ca supplement significantly improved Ca content and bone strength of the tibia. In micro-computed tomography analysis, 1% Ca supplement attenuated OVX- and low Ca-associated changes in bone mineral density, trabecular thickness, spacing and number...
May 17, 2017: Nutrients
https://www.readbyqxmd.com/read/28508358/degradomics-in-neurotrauma-profiling-traumatic-brain-injury
#7
Hadi Abou-El-Hassan, Fares Sukhon, Edwyn Jeremy Assaf, Hisham Bahmad, Hussein Abou-Abbass, Hussam Jourdi, Firas H Kobeissy
Degradomics has recently emerged as a subdiscipline in the omics era with a focus on characterizing signature breakdown products implicated in various disease processes. Driven by promising experimental findings in cancer, neuroscience, and metabolomic disorders, degradomics has significantly promoted the notion of disease-specific "degradome." A degradome arises from the activation of several proteases that target specific substrates and generate signature protein fragments. Several proteases such as calpains, caspases, cathepsins, and matrix metalloproteinases (MMPs) are involved in the pathogenesis of numerous diseases that disturb the physiologic balance between protein synthesis and protein degradation...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28506283/prolactin-blocks-the-expression-of-receptor-activator-of-nuclear-factor-%C3%AE%C2%BAb-ligand-and-reduces-osteoclastogenesis-and-bone-loss-in-murine-inflammatory-arthritis
#8
Maria G Ledesma-Colunga, Norma Adán, Georgina Ortiz, Mariana Solís-Gutiérrez, Fernando López-Barrera, Gonzalo Martínez de la Escalera, Carmen Clapp
BACKGROUND: Prolactin (PRL) reduces joint inflammation, pannus formation, and bone destruction in rats with polyarticular adjuvant-induced arthritis (AIA). Here, we investigate the mechanism of PRL protection against bone loss in AIA and in monoarticular AIA (MAIA). METHODS: Joint inflammation, trabecular bone loss, and osteoclastogenesis were evaluated in rats with AIA treated with PRL (via osmotic minipumps) and in mice with MAIA that were null (Prlr-/-) or not (Prlr+/+) for the PRL receptor...
May 15, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28505146/upregulated-autophagy-in-sertoli-cells-of-ethanol-treated-rats-is-associated-with-induction-of-inducible-nitric-oxide-synthase-inos-androgen-receptor-suppression-and-germ-cell-apoptosis
#9
Akio Horibe, Nabil Eid, Yuko Ito, Hitomi Hamaoka, Yoshihisa Tanaka, Yoichi Kondo
This study was conducted to investigate the autophagic response of Sertoli cells (SCs) to acute ethanol toxicity using in vivo and in vitro models. Adult Wistar rats were intraperitoneally injected with either 5 g/kg ethanol or phosphate-buffered saline (for the control group) and sacrificed 0, 3, 6 and 24 h after injection. Compared to the control group, enhanced germ cell apoptosis was observed in the ethanol-treated rats (ETRs) in association with upregulation of iNOS and reduced expression of androgen receptor protein levels in SCs, which were resistant to apoptosis...
May 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28505110/green-tea-polyphenols-mimicking-the-effects-of-dietary-restriction-ameliorate-high-fat-diet-induced-kidney-injury-via-regulating-autophagy-flux
#10
Xiao Xie, Weijie Yi, Piwei Zhang, Nannan Wu, Qiaoqiao Yan, Hui Yang, Chong Tian, Siyun Xiang, Miying Du, Eskedar Getachew Assefa, Xuezhi Zuo, Chenjiang Ying
Epidemiological and experimental studies reveal that Western dietary patterns contribute to chronic kidney disease, whereas dietary restriction (DR) or dietary polyphenols such as green tea polyphenols (GTPs) can ameliorate the progression of kidney injury. This study aimed to investigate the renal protective effects of GTPs and explore the underlying mechanisms. Sixty Wistar rats were randomly divided into 6 groups: standard diet (STD), DR, high-fat diet (HFD), and three diets plus 200 mg/kg(bw)/day GTPs, respectively...
May 14, 2017: Nutrients
https://www.readbyqxmd.com/read/28502922/design-synthesis-and-structure-activity-relationship-study-of-epoxysuccinyl-peptide-derivatives-as-cathepsin-b-inhibitors
#11
Xiaoye Zhang, Xiaohong Yang, Hongqiang Wang, Song Li, Kun Guo, Dan Jiang, Junhai Xiao, Di Liang
Cathepsin B is a lysosomal cysteine protease involved in many diseases. The present research demonstrates that derivatives of epoxysuccinyl-peptide are effective and selective cathepsin B inhibitors. We synthesized a series of epoxysuccinyl-peptide derivatives based on the well-known cathepsin B inhibitor E64d. Specifically, we substituted the 2-methylpropane group at the R(1) position of E64d with a sulfane, such as ethyl(methyl) sulfane or benzyl(methyl) sulfane. We also designed and synthesized a library of molecules with various substituents at the R(2) position of E64d to replace 2-methylbutane...
May 13, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28502476/purkinje-cells-are-more-vulnerable-to-the-specific-depletion-of-cathepsin-d-than-to-that-of-atg7
#12
Masato Koike, Masahiro Shibata, Takehiko Sunabori, Junji Yamaguchi, Kenji Sakimura, Masaaki Komatsu, Keiji Tanaka, Yasuo Uchiyama
Neurologic phenotypes of cathepsin D (CTSD)-deficient mice, a murine model of neuronal ceroid lipofuscinoses, indicate the importance of CTSD for the maintenance of metabolism in central nervous system neurons. To further understand the role of CTSD in central nervous system neurons, we generated mice with a CTSD deficiency specifically in the Purkinje cells (PCs) (CTSD(Flox/Flox);GRID2-Cre) and compared their phenotypes with those of PC-selective Atg7-deficient (Atg7(Flox/Flox);GRID2-Cre) mice. In both strains of mice, PCs underwent degeneration, but the CTSD-deficient PCs disappeared more rapidly than their Atg7-deficient counterparts...
May 11, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28502475/cyst-like-osteolytic-formations-in-recombinant-human-bone-morphogenetic-protein-2-rhbmp-2-augments-sheep-spinal-fusion
#13
Hsin Chuan Pan, Soonchul Lee, Kang Ting, Jia Shen, Chenchao Wang, Alan Nguyen, Emily A Berthiaume, Janette N Zara, A Simon Turner, Howard B Seim, Jin Hee Kwak, Xinli Zhang, Chia Soo
Multiple case reports using recombinant human bone morphogenetic protein-2 (rhBMP-2) have reported complications. However, the local adverse effects of rhBMP-2 application are not well documented. In this report we show that, in addition to promoting lumbar spinal fusion through potent osteogenic effects, rhBMP-2 augmentation promotes local cyst-like osteolytic formations in sheep trabecular bones that have undergone anterior lumbar interbody fusion. Three months after operation, conventional computed tomography showed that the trabecular bones of the rhBMP-2 application groups could fuse, whereas no fusion was observed in the control group...
May 11, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28501505/sevoflurane-postconditioning-attenuates-reactive-astrogliosis-and-glial-scar-formation-after-ischemia-reperfusion-brain-injury
#14
Yong-Ming Zhu, Xue Gao, Yong Ni, Wei Li, Thomas A Kent, Shi-Gang Qiao, Chen Wang, Xiao-Xuan Xu, Hui-Ling Zhang
Cerebral ischemia leads to astrocyte's activation and glial scar formation. Glial scar can inhibit axonal regeneration during the recovery phase. It has demonstrated that sevoflurane has neuroprotective effects against ischemic stroke, but its effects on ischemia-induced formation of astrogliosis and glial scar are unknown. This study was designed to investigate the effect of sevoflurane postconditioning on astrogliosis and glial scar formation in ischemic stroke model both in vivo and in vitro. The results showed that 2...
May 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/28501446/the-involvement-of-cathepsin-f-gene-ctsf-in-turbot-scophthalmus-maximus-l-mucosal-immunity
#15
Chengbin Gao, Qiang Fu, Baofeng Su, Huanhuan Song, Shun Zhou, Fenghua Tan, Chao Li
Cathepsin F (CTSF) is a recently described papain-like cysteine protease and unique among cathepsins due to an elongated N-terminal pro-region, which contains a cystatin domain. CTSF likely plays a regulatory role in processing the invariant chain which is associated with the major histocompatibility complex (MHC) class II. In this regard, we identified the CTSF gene of turbot as well as its protein structure, phylogenetic relationships, and expression patterns in mucosal tissues following Vibrio anguillarum and Streptococcus iniae challenge...
May 10, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28500840/cystatin-c-deficiency-suppresses-tumor-growth-in-a-breast-cancer-model-through-decreased-proliferation-of-tumor-cells
#16
Janja Završnik, Miha Butinar, Mojca Trstenjak Prebanda, Aleksander Krajnc, Robert Vidmar, Marko FonoviÄ, Anders Grubb, Vito Turk, Boris Turk, Olga Vasiljeva
Cysteine cathepsins are proteases that, in addition to their important physiological functions, have been associated with multiple pathologies, including cancer. Cystatin C (CstC) is a major endogenous inhibitor that regulates the extracellular activity of cysteine cathepsins. We investigated the role of cystatin C in mammary cancer using CstC knockout mice and a mouse model of breast cancer induced by expression of the polyoma middle T oncoprotein (PyMT) in the mammary epithelium. We showed that the ablation of CstC reduced the rate of mammary tumor growth...
April 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28499850/skeletal-muscle-protease-activities-in-the-early-growth-and-development-of-wild-atlantic-salmon-salmo-salar-l
#17
Liudmila A Lysenko, Nadezda P Kantserova, Elena I Kaivarainen, Marina Yu Krupnova, Nina N Nemova
Growth-related dynamics of intracellular protease activities in four year classes of the Atlantic salmon (Salmo salar L. 1758) parr and smolts inhabiting salmon rivers of northwestern Russia (the White Sea basin) were studied. Cathepsin B, cathepsin D, proteasome, and calpain activities in the skeletal muscles of salmon were assessed to investigate their relative contribution to the total protein degradation as well as to young fish growth process. It was confirmed that calpain activity dominate in salmon muscles while proteasome plays a minor role, in contrast to terrestrial vertebrates...
May 9, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/28495172/cysteine-cathepsins-b-and-x-promote-epithelial-mesenchymal-transition-of-tumor-cells
#18
Ana Mitrović, Urša Pečar Fonović, Janko Kos
Cathepsins B and X are lysosomal cysteine carboxypeptidases suggested as having a redundant role in cancer. They are involved in a number of processes leading to tumor progression but their role in the epithelial-mesenchymal transition (EMT) remains unknown. We have investigated the contribution of both cathepsins B and X in EMT using tumor cell lines differing in their expression of epithelial and mesenchymal markers and cell morphology. Higher levels of both cathepsins are shown to promote EMT and are associated with the mesenchymal-like cell phenotype...
April 25, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28493068/cathepsin-s-increases-tau-oligomer-formation-through-limited-cleavage-but-only-il-6-not-cathespin-s-serum-levels-correlate-with-disease-severity-in-the-neurodegenerative-tauopathy-progressive-supranuclear-palsy
#19
Georg Nübling, M Schuberth, K Feldmer, A Giese, L M Holdt, D Teupser, S Lorenzl
Limited cleavage promotes the aggregation propensity of protein tau in neurodegenerative tauopathies. Cathepsin S (CatS) is overexpressed in brains of patients suffering from tauopathies such as Alzheimer's disease (AD). Furthermore, CatS serum levels correlate with survival in the elderly. The current study investigates whether limited cleavage by CatS promotes tau aggregation, and whether CatS serum levels may correlate with disease severity in tauopathies. Oligomer formation of fluorescently labeled protein tau was monitored by single particle fluorescence spectroscopy after coincubation with CatS...
May 10, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28490587/heparanase-upregulation-contributes-to-porcine-reproductive-and-respiratory-syndrome-virus-release
#20
Chunhe Guo, Zhenbang Zhu, Yang Guo, Xiaoying Wang, Piao Yu, Shuqi Xiao, Yaosheng Chen, Yongchang Cao, Xiaohong Liu
Porcine reproductive and respiratory syndrome virus (PRRSV) continues to cause substantial economic losses to the pig industry worldwide. Heparan sulfate (HS) is used by PRRSV for initial attachment to target cells. However, the role of HS in the late phase of PRRSV infection and the mechanism of virus release from host cells remain largely unknown. In this study, we showed that PRRSV infection caused a decrease of HS expression and upregulated heparanase, the only known enzyme capable to degrade HS. We subsequently demonstrated that the NF-κB signaling pathway and cathepsin L protease were involved in regulation of PRRSV infection-induced heparanase...
May 10, 2017: Journal of Virology
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