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https://www.readbyqxmd.com/read/28210622/epigenetics-and-signaling-pathways-in-glaucoma
#1
REVIEW
Angela C Gauthier, Ji Liu
Glaucoma is the most common cause of irreversible blindness worldwide. This neurodegenerative disease becomes more prevalent with aging, but predisposing genetic and environmental factors also contribute to increased risk. Emerging evidence now suggests that epigenetics may also be involved, which provides potential new therapeutic targets. These three factors work through several pathways, including TGF-β, MAP kinase, Rho kinase, BDNF, JNK, PI-3/Akt, PTEN, Bcl-2, Caspase, and Calcium-Calpain signaling. Together, these pathways result in the upregulation of proapoptotic gene expression, the downregulation of neuroprotective and prosurvival factors, and the generation of fibrosis at the trabecular meshwork, which may block aqueous humor drainage...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28202907/calpain-1-deletion-impairs-mglur-dependent-ltd-and-fear-memory-extinction
#2
Guoqi Zhu, Victor Briz, Jeff Seinfeld, Yan Liu, Xiaoning Bi, Michel Baudry
Recent studies indicate that calpain-1 is required for the induction of long-term potentiation (LTP) elicited by theta-burst stimulation in field CA1 of hippocampus. Here we determined the contribution of calpain-1 in another type of synaptic plasticity, the long-term depression (LTD) elicited by activation of type-I metabotropic glutamate receptors (mGluR-LTD). mGluR-LTD was associated with calpain-1 activation following T-type calcium channel opening, and resulted in the truncation of a regulatory subunit of PP2A, B56α...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28192534/sm-p80-based-schistosomiasis-vaccine-mediated-epistatic-interactions-identified-potential-immune-signatures-for-vaccine-efficacy-in-mice-and-baboons
#3
Juan U Rojo, Michael W Melkus, Kameswara Rao Kottapalli, Oscar E Okiya, Justin Sudduth, Weidong Zhang, Adebayo J Molehin, Darrick Carter, Afzal A Siddiqui
Schistosomiasis is a neglected parasitic disease of major public health concern as it affects over 250 million people in developing countries. Currently there is no licensed vaccine available against schistosomiasis. The Schistosoma mansoni calpain protein, Sm-p80, is a leading vaccine candidate now ready to move to clinical trials. In order to better assess Sm-p80 vaccine immunogenicity; here we used a systems biology approach employing RNA-sequencing to identify gene signatures and epistatic interactions following Sm-p80 vaccination in mouse and baboon models that may predict vaccine efficacy...
2017: PloS One
https://www.readbyqxmd.com/read/28192161/enzymatic-cleavage-of-myoferlin-releases-a-dual-c2-domain-module-linked-to-erk-signalling
#4
Ann-Katrin Piper, Samuel E Ross, Gregory M Redpath, Frances A Lemckert, Natalie Woolger, Adam Bournazos, Peter A Greer, Roger B Sutton, Sandra T Cooper
Myoferlin and dysferlin are closely related members of the ferlin family of Ca(2+)-regulated vesicle fusion proteins. Dysferlin is proposed to play a role in Ca(2+)-triggered vesicle fusion during membrane repair. Myoferlin regulates endocytosis, recycling of growth factor receptors and adhesion proteins, and is linked to the metastatic potential of cancer cells. Our previous studies establish that dysferlin is cleaved by calpains during membrane injury, with the cleavage motif encoded by alternately-spliced exon 40a...
February 10, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28190474/salvianolic-acid-a-inhibits-calpain-activation-and-enos-uncoupling-during-focal-cerebral-ischemia-in-mice
#5
Qaisar Mahmood, Guang-Fa Wang, Gang Wu, Huan Wang, Chang-Xin Zhou, Hong-Yu Yang, Zhi-Rong Liu, Feng Han, Kui Zhao
BACKGROUND: Salvianolic acid A (SAA) is obtained from Chinese herb Salviae Miltiorrhizae Bunge (Labiatae), has been reported to have the protective effects against cardiovascular and neurovascular diseases. HYPOTHESIS: The aim of present study was to investigate the relationship between the effectiveness of SAA against neurovascular injury and its effects on calpain activation and endothelial nitric oxide synthase (eNOS) uncoupling. STUDY DESIGN: SAA or vehicle was given to C57BL/6 male mice for seven days before the occlusion of middle cerebral artery (MCAO) for 60min...
February 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28182699/bifunctional-effects-of-o-methylated-flavones-from-scutellaria-baicalensis-georgi-on-melanocytes-inhibition-of-melanin-production-and-intracellular-melanosome-transport
#6
Michiko Kudo, Kumiko Kobayashi-Nakamura, Kentaro Tsuji-Naito
The growing interest in skin lightening has recently renewed attention on the esthetic applications of Chinese herbal medicine. Although Scutellaria baicalensis Georgi is used for antipyretic and antiinflammatory purposes, its whitening effect remains unclear. This study reports three major findings: (1) S. baicalensis has a potent inhibitory effect on melanogenesis; (2) wogonin and its glycoside are the active components of S. baicalensis; and (3) O-methylated flavones from S. baicalensis, such as wogonin, inhibit intracellular melanosome transport...
2017: PloS One
https://www.readbyqxmd.com/read/28179558/cell-specific-pkm-isoforms-contribute-to-the-maintenance-of-different-forms-of-persistent-long-term-synaptic-plasticity
#7
Jiangyuan Hu, Kerry Adler, Carole Abi Farah, Margaret H Hastings, Wayne S Sossin, Samuel Schacher
Multiple kinase activations contribute to long-term synaptic plasticity, a cellular mechanism mediating long-term memory. The sensorimotor synapse of Aplysia expresses different forms of long-term facilitation (LTF) - non-associative and associative LTF - that require the timely activation of kinases, including PKC. It is not known which PKC isoforms in the sensory neuron or motor neuron L7 are required to sustain each form of LTF. We show that different PKMs, the constitutively active isoforms of PKCs generated by calpain cleavage, in the sensory neuron and L7 are required to maintain each form of LTF...
February 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28173805/serum-proteomic-profiles-in-ckcs-with-mitral-valve-disease
#8
Chiara Locatelli, Cristian Piras, Giulia Riscazzi, Isabella Alloggio, Ilaria Spalla, Alessio Soggiu, Viviana Greco, Luigi Bonizzi, Paola Roncada, Paola G Brambilla
BACKGROUND: Myxomatous mitral valve disease (MVD) is the most common acquired heart disease in dogs, and the Cavalier King Charles Spaniel (CKCS) is the most studied breed because of the high prevalence, early onset and hereditary component evidenced in the breed. MVD has different severity levels, and there are many practical limitations in identifying its asymptomatic stages. Proteomic techniques are valuable for studying the proteins and peptides involved in cardiovascular diseases, including the period prior to the clinical onset of the disease...
February 7, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28166119/muscle-protein-turnover-and-the-molecular-regulation-of-muscle-mass-during-hypoxia
#9
Stefan M Pasiakos, Claire E Berryman, Christopher T Carrigan, Andrew J Young, John W Carbone
Effects of environmental hypoxia on fat-free mass are well studied. Negative energy balance, increased nitrogen excretion and fat-free mass loss are commonly observed in lowlanders sojourning at high altitude. Reductions in fat-free mass can be minimized if energy consumption matches energy expenditure. However, in non-research settings, achieving energy balance during high altitude sojourns is unlikely and myofibrillar protein mass is usually lost, but the mechanisms accounting for the loss of muscle mass are not clear...
February 4, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28163253/apoptotic-death-in-erythrocytes-of-lamprey-lampetra-fluviatilis-induced-by-ionomycin-and-tert-butyl-hydroperoxide
#10
Natalia I Agalakova, Tatiana I Ivanova, Gennadii P Gusev, Anna V Nazarenkova, Dina A Sufieva
The work examined the effects of Ca(2+) overload and oxidative damage on erythrocytes of river lamprey Lampetra fluvialtilis. The cells were incubated for 3h with 0.1-5μM Ca(2+) ionophore ionomycin in combination with 2.5mM Ca(2+) and 10-100μM pro-oxidant agent tert-butyl hydroperoxide (tBHP). The sensitivity of lamprey RBCs to studied compounds was evaluated by the kinetics of their death. Both toxicants induced dose- and time dependent phosphatidylserine (PS) externalization (annexin V-FITC labeling) and loss of membrane integrity (propidium iodide uptake)...
February 2, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/28137470/nitroimidazole-derivatives-of-polypyridyl-ruthenium-complexes-towards-understanding-their-anticancer-activity-and-mode-of-action
#11
Olga Mazuryk, Oksana Krysiak-Foria, Agnieszka Żak, Franck Suzenet, Agata Ptak-Belowska, Tomasz Brzozowski, Grażyna Stochel, Małgorzata Brindell
The mechanism of cell death induced by the ruthenium polypyridyl complexes comprising two 4,7-diphenyl-1,10-phenanthroline ligands as well as one unmodified 2,2'-bipyridyl or modified with 2-nitroimidazole moiety attached by shorter (C3H6) or longer (C6H12) linker was investigated. Cytotoxicity and proliferation assays revealed that the studied Ru polypyridyl complexes are more toxic against human pancreas carcinoma PANC-1 cell line than normal human keratinocytes HaCaT with IC50 of 3-5μM. The Ru complexes despite accumulation in mitochondria do not lead to mitochondrial disfunction, though decreasing of mitochondrial Ca(2+) causes mitochondria membrane hyperpolarization...
January 28, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28131390/calpain-14-and-its-association-with-eosinophilic-esophagitis
#12
REVIEW
Vladislav A Litosh, Mark Rochman, Jeffrey K Rymer, Aleksey Porollo, Leah C Kottyan, Marc E Rothenberg
Calpains are a family of intracellular, calcium-dependent cysteine proteases involved in a variety of regulatory processes, including cytoskeletal dynamics, cell-cycle progression, signal transduction, gene expression, and apoptosis. These enzymes have been implicated in a number of disease processes, notably for this review involving eosinophilic tissue inflammation, such as eosinophilic esophagitis (EoE), a chronic inflammatory disorder triggered by allergic hypersensitivity to food and associated with genetic variants in calpain 14 (CAPN14)...
January 25, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28130160/chelerythrine-promotes-ca-2-dependent-calpain-activation-in-neuronal-cells-in-a-pkc-independent-manner
#13
Ana Saavedra, Sara Fernández-García, Silvia Cases, Mar Puigdellívol, Rafael Alcalá-Vida, Núria Martín-Flores, Jordi Alberch, Silvia Ginés, Cristina Malagelada, Esther Pérez-Navarro
BACKGROUND: Chelerythrine is widely used as a broad range protein kinase C (PKC) inhibitor, but there is controversy about its inhibitory effect. Moreover, it has been shown to exert PKC-independent effects on non-neuronal cells. METHODS: In this study we investigated possible off-target effects of chelerythrine on cultured cortical rodent neurons and a neuronal cell line. RESULTS: We found that 10μM chelerythrine, a commonly used concentration in neuronal cultures, reduces PKC and cAMP-dependent protein kinase substrates phosphorylation in mouse cultured cortical neurons, but not in rat primary cortical neurons or in a striatal cell line...
January 24, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28112357/calpain-inhibitors-ameliorate-muscle-wasting-in-a-cachectic-mouse-model-bearing-ct26-colorectal-adenocarcinoma
#14
Xing-Yu Lin, Si-Zeng Chen
Cancer-related cachexia involves increased protein breakdown through various proteolytic pathways, including the ubiquitin-proteasome pathway (UPP). We hypothesized that a calcium- and calpain-dependent pathway might play a crucial role during the proteolytic procedure, and that pathway interventions would ameliorate cancer cachexia in vivo. After being inoculated with CT26 adenocarcinoma cell culture subcutaneously, BALB/c mice developed cachexia in 12 days. They were then administered with different types of calpain inhibitors individually or in combination for 7 consecutive days...
January 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28112201/novel-bioinformatics-based-approach-for-proteomic-biomarkers-prediction-of-calpain-2-caspase-3-protease-fragmentation-application-to-%C3%AE-ii-spectrin-protein
#15
Atlal El-Assaad, Zaher Dawy, Georges Nemer, Firas Kobeissy
The crucial biological role of proteases has been visible with the development of degradomics discipline involved in the determination of the proteases/substrates resulting in breakdown-products (BDPs) that can be utilized as putative biomarkers associated with different biological-clinical significance. In the field of cancer biology, matrix metalloproteinases (MMPs) have shown to result in MMPs-generated protein BDPs that are indicative of malignant growth in cancer, while in the field of neural injury, calpain-2 and caspase-3 proteases generate BDPs fragments that are indicative of different neural cell death mechanisms in different injury scenarios...
January 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28110215/neuroprotective-action-of-n-acetyl-serotonin-in-oxidative-stress-induced-apoptosis-through-the-activation-of-both-trkb-creb-bdnf-pathway-and-akt-nrf2-antioxidant-enzyme-in-neuronal-cells
#16
Jae-Myung Yoo, Bo Dam Lee, Dai-Eun Sok, Jin Yuel Ma, Mee Ree Kim
N-acetyl serotonin (NAS) as a melatonin precursor has neuroprotective actions. Nonetheless, it is not clarified how NAS protects neuronal cells against oxidative stress. Recently, we have reported that N-palmitoyl serotonins possessed properties of antioxidants and neuroprotection. Based on those, we hypothesized that NAS, a N-acyl serotonin, may have similar actions in oxidative stress-induced neuronal cells, and examined the effects of NAS based on in vitro and in vivo tests. NAS dose-dependently inhibited oxidative stress-induced cell death in HT-22 cells...
January 6, 2017: Redox Biology
https://www.readbyqxmd.com/read/28108289/negative-feedback-regulation-between-microrna-let-7g-and-lox-1-mediated-hypoxia-induced-pasmcs-proliferation
#17
Wei-Fang Zhang, Tian-Tian Zhu, You-Wen Xiong, Ai-Zhen Xiong, Xiao-Yue Ge, Chang-Ping Hu, Zheng Zhang
BACKGROUND: Pulmonary hypertension (PH) is a proliferative disorder associated with enhanced proliferation and suppressed apoptosis of pulmonary artery smooth muscle cells (PASMCs). Our lately study demonstrated that let-7g inhibited hypoxia-induced proliferation of PASMCs via repressed c-myc-Bmi-1-p16 signaling pathway. However, the upstream of let-7g has not yet been fully defined. Previous studies have shown that LOX-1, a target of let-7g, could also regulate the expression of let-7g in human aortic endothelial cells...
January 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28107862/neuroprotective-effect-of-spilanthes-acmella-murr-on-pesticide-induced-neuronal-cells-death
#18
Wilasinee Suwanjang, Bongkot Khongniam, Sujittra Srisung, Supaluk Prachayasittikul, Virapong Prachayasittikul
OBJECTIVE: To investigate protective effects of Spilanthes acmella (S. acmella) Murr. extracts against pesticide-induced neuronal cells death and to elucidate the underlying molecular mechanism in dopaminergic (SH-SY5Y) cells lines. METHODS: Cell viability of SH-SY5Y cells was studied by treating the cells with various concentration of pirimicarb for 24 h. Neuroprotective effect of S. acmella Murr. extracts was investigated by adding the plant extracts to the medium for 24 h prior to the incubation with 100 μM H2O2 or with pirimicarb for 24 h...
January 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28104436/capsaicin-synergizes-with-camptothecin-to-induce-increased-apoptosis-in-human-small-cell-lung-cancers-via-the-calpain-pathway
#19
Jamie R Friedman, Haley E Perry, Kathleen C Brown, Ying Gao, Ju Lin, Cathyrn D Stevenson, John D Hurley, Nicholas A Nolan, Austin T Akers, Yi Charlie Chen, Krista L Denning, Linda G Brown, Piyali Dasgupta
Small cell lung cancer (SCLC) is characterized by excellent initial response to chemotherapy and radiation therapy with a majority of the patients showing tumor shrinkage and even remission. However, the challenge with SCLC therapy is that patients inevitably relapse and subsequently do not respond to the first line treatment. Recent clinical studies have investigated the possibility of camptothecin-based combination therapy as first line treatment for SCLC patients. Conventionally, camptothecin is used for recurrent SCLC and has poor survival outcomes...
January 16, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28103310/epidemiological-and-molecular-characterization-of-a-mexican-population-isolate-with-high-prevalence-of-limb-girdle-muscular-dystrophy-type-2a-due-to-a-novel-calpain-3-mutation
#20
Carlos A Pantoja-Melendez, Antonio Miranda-Duarte, Bladimir Roque-Ramirez, Juan C Zenteno
Limb-Girdle Muscular Dystrophy type 2 (LGMD2) is a group of autosomally recessive inherited disorders defined by weakness and wasting of the shoulder and pelvic girdle muscles. In the past, several population isolates with high incidence of LGMD2 arising from founder mutation effects have been identified. The aim of this work is to describe the results of clinical, epidemiologic, and molecular studies performed in a Mexican village segregating numerous cases of LGMD2. A population census was conducted in the village to identify all LGMD affected patients...
2017: PloS One
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