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cathepsin d

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https://www.readbyqxmd.com/read/28096236/inhibitory-effects-of-%C3%AE-and-%C3%AE-tocopherols-on-estrogen-stimulated-breast-cancer-in-vitro-and-in-vivo
#1
Min Ji Bak, Soumyasri Das Gupta, Joseph Wahler, Hong Jin Lee, Xiaowei Li, Mao-Jung Lee, Chung S Yang, Nanjoo Suh
Estrogens have been implicated as complete carcinogens for breast and other tissues through mechanisms involving increased cell proliferation, oxidative stress and DNA damage. Because of their potent antioxidant activity and other effects, tocopherols have been shown to exert anti-tumor activities in various cancers. However, limited information is available on the effect of different forms of tocopherols in estrogen-mediated breast cancer. To address this, we examined the effects of α-, γ- and δ-tocopherols as well as a natural γ-tocopherol rich mixture of tocopherols, γ-TmT, on estrogen-stimulated MCF-7 cells in vitro and in vivo...
January 17, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28087651/frontline-science-multiple-cathepsins-promote-inflammasome-independent-particle-induced-cell-death-during-nlrp3-dependent-il-1%C3%AE-activation
#2
Gregory M Orlowski, Shruti Sharma, Jeff D Colbert, Matthew Bogyo, Stephanie A Robertson, Hiroshi Kataoka, Francis K Chan, Kenneth L Rock
Sterile particles cause several chronic, inflammatory diseases, characterized by repeating cycles of particle phagocytosis and inflammatory cell death. Recent studies have proposed that these processes are driven by the NLRP3 inflammasome, a platform activated by phagocytosed particles, which controls both caspase-1-dependent cell death (pyroptosis) and mature IL-1β secretion. After phagocytosis, particles can disrupt lysosomes, and inhibitor studies have suggested that the resulting release of a lysosomal protease-cathepsin B-into the cytosol somehow activates NLRP3...
January 13, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28078611/hyperbaric-oxygen-prevents-cognitive-impairments-in-mice-induced-by-d-galactose-by-improving-cholinergic-and-anti-apoptotic-functions
#3
Chunxia Chen, Luying Huang, Zhihuan Nong, Yaoxuan Li, Wan Chen, Jianping Huang, Xiaorong Pan, Guangwei Wu, Yingzhong Lin
Our previous study demonstrated that hyperbaric oxygen (HBO) improved cognitive impairments mainly by regulating oxidative stress, inflammatory responses and aging-related gene expression. However, a method for preventing cognitive dysfunction has yet to be developed. In the present study, we explored the protective effects of HBO on the cholinergic system and apoptosis in D-galactose (D-gal)-treated mice. A model of aging was established via systemic intraperitoneal injection of D-gal daily for 8 weeks. HBO was administered during the last 2 weeks of D-gal injection...
January 11, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28077330/dehydropachymic-acid-decreases-bafilomycin-a1-induced-%C3%AE-amyloid-accumulation-in-pc12-cells
#4
Mengyao Yu, Xiaoyan Xu, Nan Jiang, Wei Wei, Fang Li, Liming He, Xia Luo
ETHNOPHARMACOLOGICAL RELEVANCE: Fuling, the sclerotium of Poria cocos, was frequently used in traditional Chinese medicine (TCM) formulae for Alzheimer's disease (AD) intervention over the past 10 centuries. And its extracts exhibited significant effects in both cellular and animal models of AD in previous studies. However, its mechanisms on prevention and treatment of AD have not been well elucidated yet. AIM OF THE STUDY: To investigate the effect and corresponding mechanisms of dehydropachymic acid, which is one of the major triterpenes in Poria cocos, on the clearance of β-Amyloid accumulation in bafilomycin A1 induced PC12 cells...
January 7, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28073925/progranulin-regulates-lysosomal-function-and-biogenesis-through-acidification-of-lysosomes
#5
Yoshinori Tanaka, Genjiro Suzuki, Takashi Matsuwaki, Masato Hosokawa, Geidy Serrano, Thomas G Beach, Keitaro Yamanouchi, Masato Hasegawa, Masugi Nishihara
Progranulin (PGRN) haploinsufficiency resulting from loss-of-function mutations in the PGRN gene causes frontotemporal lobar degeneration accompanied by TDP-43 accumulation, and patients with homozygous mutations in the PGRN gene present with neuronal ceroid lipofuscinosis. Although it remains unknown why PGRN deficiency causes neurodegenerative diseases, there is increasing evidence that PGRN is implicated in lysosomal functions. Here, we show PGRN is a secretory lysosomal protein that regulates lysosomal function and biogenesis by controlling the acidification of lysosomes...
January 10, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28064012/effect-of-a-novel-quaternary-ammonium-silane-on-dentin-protease-activities
#6
D Umer, C K Y Yiu, M F Burrow, L-N Niu, F R Tay
OBJECTIVES: Demineralized dentin collagen release C-terminal cross-linked telopeptide (ICTP) and C-terminal peptide (CTX) during degradation. The present study evaluated the effects of dentin pre-treatment with K21, a quaternary ammonium silane (QAS), on matrix metalloproteinase (MMP) and cathepsin K-mediated collagen degradation. METHODS: Dentin beams were demineralized with 10% H3PO4 for 24h. After baseline dry mass measurements, the beams were divided into 5 groups (N=10) according to protease inhibitors...
January 4, 2017: Journal of Dentistry
https://www.readbyqxmd.com/read/28062666/cyclodextrin-has-conflicting-actions-on-autophagy-flux-in-vivo-in-brains-of-normal-and-alzheimer-model-mice
#7
Dun-Sheng Yang, Philip Stavrides, Asok Kumar, Ying Jiang, Panaiyur S Mohan, Masuo Ohno, Kostantin Dobrenis, Cristin D Davidson, Mitsuo Saito, Monika Pawlik, Chunfeng Huo, Steven U Walkley, Ralph A Nixon
2-hydroxypropyl-β-cyclodextrin (CYCLO), a modifier of cholesterol efflux from cellular membrane and endo-lysosomal compartments, reduces lysosomal lipid accumulations and has therapeutic effects in animal models of Niemann-Pick disease type C and several other neurodegenerative states. Here, we investigated CYCLO effects on autophagy in wild-type mice and TgCRND8 mice - an Alzheimer's Disease (AD) model exhibiting β-amyloidosis, neuronal autophagy deficits leading to protein and lipid accumulation within greatly enlarged autolysosomes...
January 5, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28061403/berberine-ameliorates-intrahippocampal-kainate-induced-status-epilepticus-and-consequent-epileptogenic-process-in-the-rat-underlying-mechanisms
#8
Reza Sedaghat, Yosra Taab, Zahra Kiasalari, Siamak Afshin-Majd, Tourandokht Baluchnejadmojarad, Mehrdad Roghani
Status epilepticus (SE) is a life-threatening neurologic condition, instigating epileptogenesis to transform normal brain to an epileptic condition. SE is followed by spontaneous recurrent seizures (SRS) and final development of temporal lobe epilepsy (TLE) that is resistant to treatment. Neuroprotective strategies are increasingly put forward as a promising therapy to prevent and/or manage epileptic conditions. In this study, we investigated whether berberis alkaloid, i.e. berberine (BBR), could ameliorate intrahippocampal kainate-induced SE and its consequent epileptogenic process and to explore some underlying mechanisms...
January 3, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28035917/apolipoprotein-e4-elicits-lysosomal-cathepsin-d-release-decreased-thioredoxin-1-levels-and-apoptosis
#9
Torbjörn Persson, Francesca Lattanzio, Javier Calvo-Garrido, Roberto Rimondini, Marta Rubio-Rodrigo, Erik Sundström, Silvia Maioli, Anna Sandebring-Matton, Ángel Cedazo-Mínguez
The major genetic risk factor for Alzheimer's disease (AD), apolipoprotein E4 (ApoE4), has been suggested to have detrimental effects on neurons, including direct toxicity via apoptosis. Thioredoxin-1 (Trx1) is an endogenous antioxidant protein important for redox regulation and participates in the regulation of apoptosis through the inhibition of apoptosis signal-regulating kinase-1 (Ask-1). In this study, we have investigated the effects of ApoE on Trx1 in the brain. Our results showed that the protein levels of Trx1 were reduced in the hippocampus of ApoE4 targeted replacement (TR) mice compared to ApoE3 TR mice...
December 30, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28017540/transcription-factor-eb-expression-in-early-breast-cancer-relates-to-lysosomal-autophagosomal-markers-and-prognosis
#10
Alexandra Giatromanolaki, Efthimios Sivridis, Dimitra Kalamida, Michael I Koukourakis
BACKGROUND: Disrupting the autophagic balance to trigger autophagic death may open new strategies for cancer therapy. Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and may play a role in cancer biology and clinical behavior. METHODS: The expression of TFEB and the lysosomal cancer cell content (expression of lysosomal associated membrane protein 2a [LAMP2a] and cathepsin D) was studied in a series of 100 T1-stage breast carcinomas...
November 23, 2016: Clinical Breast Cancer
https://www.readbyqxmd.com/read/28009604/renal-cell-carcinoma-with-chromosome-6p-amplification-including-the-tfeb-gene-a-novel-mechanism-of-tumor-pathogenesis
#11
Sean R Williamson, David J Grignon, Liang Cheng, Laura Favazza, Dibson D Gondim, Shannon Carskadon, Nilesh S Gupta, Dhananjay A Chitale, Shanker Kalyana-Sundaram, Nallasivam Palanisamy
Amplification of chromosome 6p has been implicated in aggressive behavior in several cancers, but has not been characterized in renal cell carcinoma (RCC). We identified 9 renal tumors with amplification of chromosome 6p including the TFEB gene, 3 by fluorescence in situ hybridization, and 6 from the Cancer Genome Atlas (TCGA) databases. Patients' ages were 28 to 78 years (median, 61 y). Most tumors were high stage (7/9 pT3a, 2/9 pN1). Using immunohistochemistry, 2/4 were positive for melanocytic markers and cathepsin K...
December 22, 2016: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27997605/role-of-myeloperoxidase-oxidants-in-the-modulation-of-cellular-lysosomal-enzyme-function-a-contributing-factor-to-macrophage-dysfunction-in-atherosclerosis
#12
Fahd O Ismael, Tessa J Barrett, Diba Sheipouri, Bronwyn E Brown, Michael J Davies, Clare L Hawkins
Low-density lipoprotein (LDL) is the major source of lipid within atherosclerotic lesions. Myeloperoxidase (MPO) is present in lesions and forms the reactive oxidants hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN). These oxidants modify LDL and have been strongly linked with the development of atherosclerosis. In this study, we examined the effect of HOCl, HOSCN and LDL pre-treated with these oxidants on the function of lysosomal enzymes responsible for protein catabolism and lipid hydrolysis in murine macrophage-like J774A...
2016: PloS One
https://www.readbyqxmd.com/read/27979096/actin-proteolysis-during-ripening-of-dry-fermented-sausages-at-different-ph-values
#13
A Berardo, B Devreese, H De Maere, D A Stavropoulou, G Van Royen, F Leroy, S De Smet
In dry fermented sausages, myofibrillar proteins undergo intense proteolysis generating small peptides and free amino acids that play a role in flavour generation. This study aimed to identify small peptides arising from actin proteolysis, as influenced by the type of processing. Two acidification profiles were imposed, in order to mimic the pH normally obtained in southern-type and northern-type dry fermented sausages. The identification of peptides was done by liquid chromatography coupled to mass spectrometry in a data-independent positive mode of acquisition (LC-MS(E))...
April 15, 2017: Food Chemistry
https://www.readbyqxmd.com/read/27933948/discovery-of-the-3-imino-1-2-4-thiadiazinane-1-1-dioxide-derivative-verubecestat-mk-8931-a-%C3%AE-site-amyloid-precursor-protein-cleaving-enzyme-1-inhibitor-for-the-treatment-of-alzheimer-s-disease
#14
Jack D Scott, Sarah W Li, Andrew P J Brunskill, Xia Chen, Kathleen Cox, Jared N Cumming, Mark Forman, Eric J Gilbert, Robert A Hodgson, Lynn A Hyde, Qin Jiang, Ulrich Iserloh, Irina Kazakevich, Reshma Kuvelkar, Hong Mei, John Meredith, Jeffrey Misiaszek, Peter Orth, Lana M Rossiter, Meagan Slater, Julie Stone, Corey O Strickland, Johannes H Voigt, Ganfeng Wang, Hongwu Wang, Yusheng Wu, William J Greenlee, Eric M Parker, Matthew E Kennedy, Andrew W Stamford
Verubecestat 3 (MK-8931), a diaryl amide-substituted 3-imino-1,2,4-thiadiazinane 1,1-dioxide derivative, is a high-affinity β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor currently undergoing Phase 3 clinical evaluation for the treatment of mild to moderate and prodromal Alzheimer's disease. Although not selective over the closely related aspartyl protease BACE2, verubecestat has high selectivity for BACE1 over other key aspartyl proteases, notably cathepsin D, and profoundly lowers CSF and brain Aβ levels in rats and nonhuman primates and CSF Aβ levels in humans...
December 8, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27929705/snapin-is-critical-for-lysosomal-acidification-and-autophagosome-maturation-in-macrophages
#15
Bo Shi, Qi-Quan Huang, Robert Birkett, Renee Doyle, Andrea Dorfleutner, Christian Stehlik, Congcong He, Richard M Pope
We previously observed that SNAPIN, which is an adaptor protein in the SNARE core complex, was highly expressed in rheumatoid arthritis synovial tissue macrophages, but its role in macrophages and autoimmunity is unknown. To identify SNAPIN's role in these cells, we employed siRNA to silence the expression of SNAPIN in primary human macrophages. Silencing SNAPIN resulted in swollen lysosomes with impaired CTSD (cathepsin D) activation, although total CTSD was not reduced. Neither endosome cargo delivery nor lysosomal fusion with endosomes or autophagosomes was inhibited following the forced silencing of SNAPIN...
December 8, 2016: Autophagy
https://www.readbyqxmd.com/read/27929536/hyperhomocysteinemia-causes-er-stress-and-impaired-autophagy-that-is-reversed-by-vitamin-b-supplementation
#16
Madhulika Tripathi, Cheng Wu Zhang, Brijesh Kumar Singh, Rohit Anthony Sinha, Kyaw Thu Moe, Deidre Anne DeSilva, Paul Michael Yen
Hyperhomocysteinemia (HHcy) is a well-known risk factor for stroke; however, its underlying molecular mechanism remains unclear. Using both mouse and cell culture models, we have provided evidence that impairment of autophagy has a central role in HHcy-induced cellular injury in the mouse brain. We observed accumulation of LC3B-II and p62 that was associated with increased MTOR signaling in human and mouse primary astrocyte cell cultures as well as a diet-induced mouse model of HHcy, HHcy decreased lysosomal membrane protein LAMP2, vacuolar ATPase (ATP6V0A2), and protease cathepsin D, suggesting that lysosomal dysfunction also contributed to the autophagic defect...
December 8, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27922112/plasma-cathepsin-d-correlates-with-histological-classifications-of-fatty-liver-disease-in-adults-and-responds-to-intervention
#17
Sofie M A Walenbergh, Tom Houben, Sander S Rensen, Veerle Bieghs, Tim Hendrikx, Patrick J van Gorp, Yvonne Oligschlaeger, Mike L J Jeurissen, Marion J J Gijbels, Wim A Buurman, Anita C E Vreugdenhil, Jan Willem M Greve, Jogchum Plat, Marten H Hofker, Satish Kalhan, Jussi Pihlajamäki, Patrick Lindsey, Ger H Koek, Ronit Shiri-Sverdlov
Non-alcoholic steatohepatitis (NASH) is characterized by liver lipid accumulation and inflammation. The mechanisms that trigger hepatic inflammation are poorly understood and subsequently, no specific non-invasive markers exist. We previously demonstrated a reduction in the plasma lysosomal enzyme, cathepsin D (CatD), in children with NASH compared to children without NASH. Recent studies have raised the concept that non-alcoholic fatty liver disease (NAFLD) in adults is distinct from children due to a different histological pattern in the liver...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27913947/preclinical-evaluation-of-cathepsin-based-fluorescent-imaging-system-for-cytoreductive-surgery
#18
Carlos H F Chan, Lukas F Liesenfeld, Isabel Ferreiro-Neira, James C Cusack
BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is a treatment option for peritoneal surface malignancies. The ability to detect microscopic foci of peritoneal metastasis intraoperatively may ensure the completeness of cytoreduction. In this study, we evaluated the suitability of a hand-held cathepsin-based fluorescent imaging system for intraoperative detection of appendiceal and colorectal peritoneal metastasis. METHODS: Peritoneal tumors and normal peritoneal tissues were collected from patients with appendiceal and colorectal peritoneal metastasis...
December 2, 2016: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/27908708/chlorogenic-acid-ameliorates-isoproterenol-induced-myocardial-injury-in-rats-by-stabilizing-mitochondrial-and-lysosomal-enzymes
#19
Palaniyandi Akila, Lourthurani Asaikumar, Lakshmanan Vennila
This study was deliberated to aspire the effects of chlorogenic acid (CGA) against myocardial infarction (MI) induced by Isoproterenol (ISO), in a rat model. In the pathology of MI, enzymes released due to the mitochondrial and lysosomal lipid peroxidation play an integral role. Induction of rats with ISO (85mg/kg BW) for 2 consecutive days resulted in a significant decrease in the activities of heart mitochondrial enzymes isocitrate dehydrogenase (ICDH), α-ketoglutarate dehydrogenase (α-KGDH), succinate dehydrogenase (SDH) and malate dehydrogenase (MDH)...
January 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27903071/reduced-levels-and-bioactivity-of-endogenous-protease-cathepsin-d-in-genital-tract-secretions-of-postmenopausal-women
#20
Mariel Jais, Naji Younes, Stacey Chapman, Susan Cu-Uvin, Mimi Ghosh
PROBLEM: HIV infections are increasing in older adult populations. Although it is known that the HIV/AIDS epidemics affect women disproportionately, little is known regarding immune responses in reproductive tract of postmenopausal women, specifically regarding endogenous proteases that modulate inflammation, tissue remodeling and wound healing. METHOD OF STUDY: Levels and bioactivity of endogenous proteases Cathepsin B, D, G, and Neutrophil Elastase were measured in cervical vaginal lavage collected from 20 HIV-negative pre- and postmenopausal women...
November 30, 2016: AIDS Research and Human Retroviruses
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