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https://www.readbyqxmd.com/read/28808241/specific-calpain-inhibition-protects-kidney-against-inflammaging
#1
Guillaume Hanouna, Laurent Mesnard, Sophie Vandermeersch, Joëlle Perez, Sandrine Placier, Jean-Philippe Haymann, Fabien Campagne, Julien Moroch, Aurélien Bataille, Laurent Baud, Emmanuel Letavernier
Calpains are ubiquitous pro-inflammatory proteases, whose activity is controlled by calpastatin, their specific inhibitor. Transgenic mice over-expressing rabbit calpastatin (CalpTG) are protected against vascular remodelling and angiotensin II-dependent inflammation. We hypothesized that specific calpain inhibition would protect against aging-related lesions in arteries and kidneys. We analysed tissues from 2-months and 2-years-old CalpTG and wild-type mice and performed high throughput RNA-Sequencing of kidney tissue in aged mice...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801351/calcium-induced-calpain-mediates-apoptosis-via-caspase-3-in-a-mouse-photoreceptor-cell-line
#2
Ashish K Sharma, Baerbel Rohrer
No abstract text is available yet for this article.
August 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28801169/a-single-high-dose-of-dexamethasone-increases-gap-43-and-synaptophysin-in-the-hippocampus-of-aged-rats
#3
Vesna Tesic, Milka Perovic, Ivan Zaletel, Mirna Jovanovic, Nela Puskas, Sabera Ruzdijic, Selma Kanazir
The administration of dexamethasone, a synthetic glucocorticoid receptor agonist, has been reported to modulate cognitive performance in both animals and humans. In the present study, we demonstrate the effects of a single high dose of dexamethasone on the expression and distribution of synaptic plasticity-related proteins, growth-associated protein-43 (GAP-43) and synaptophysin, in the hippocampus of 6-, 12-, 18- and 24-month-old rats. Acute dexamethasone treatment significantly altered the expression of GAP-43 at the posttranslational level by modulating the levels of phosphorylated GAP-43 and proteolytic GAP-43-3 fragment...
August 8, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28800153/increased-autolysis-of-%C3%AE-calpain-in-skeletal-muscles-of-chronic-alcohol-fed-rats
#4
Yulia V Gritsyna, Nikolay N Salmov, Alexander G Bobylev, Anna D Ulanova, Nikolay I Kukushkin, Zoya A Podlubnaya, Ivan M Vikhlyantsev
BACKGROUND: Proteolysis can proceed via several distinct pathways such as the lysosomal, calcium-dependent, and ubiquitin (Ub)-proteasome-dependent pathways. Calpains are the main proteases that cleave a large variety of proteins, including the giant sarcomeric proteins titin and nebulin. Chronic ethanol feeding for 6 weeks did not affect the activities of μ-calpain and m-calpain in the m. gastrocnemius. In our research, changes in μ-calpain activity were studied in the m. gastrocnemius and m...
August 11, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28789934/targeting-calpains-a-novel-immunomodulatory-approach-for-microbial-infections
#5
REVIEW
Vijay Kumar, Ahmad Ali
Calpains are a family of Ca(2+) dependent cytosolic non-lysosomal proteases with well conserved cysteine-rich domains for enzymatic activity. Due to their functional dependency on Ca(2+) concentrations, they are involved in various cellular processes that are regulated by intracellular ca(2+) concentration (i.e. embryo development, cell development and migration, maintenance of cellular architecture and structure etc.). Calpains are widely studied proteases in mammalian (i.e. mouse and human) physiology and pathophysiology due to their ubiquitous presence...
August 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28764914/breaking-down-autophagy-and-the-ubiquitin-proteasome-system
#6
Shinae Jung, Yuhyun Chung, Young J Oh
Autophagy is an evolutionarily conserved catabolic process that is involved in cellular homeostasis and stress responses. Although basal levels of autophagy are essential for cellular homeostasis, dysregulated autophagy is linked to neurodegeneration. Recent studies using genetic or neurotoxin-based models of Parkinson's disease (PD) detect autophagy. We demonstrate that neurotoxins induce autophagy in dopaminergic neuronal cell line and primary cultured neurons. Based on previous reports, including ones from our laboratory, which show that elevated reactive oxygen species (ROS) and cytosolic calcium are implicated in dopaminergic neurodegeneration, we reasoned that these triggers may play critical roles in determining dysregulated autophagy...
July 26, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28763058/a-novel-preventive-therapy-for-paclitaxel-induced-cognitive-deficits-preclinical-evidence-from-c57bl-6-mice
#7
P Huehnchen, W Boehmerle, A Springer, D Freyer, M Endres
Chemotherapy-induced central nervous system (CNS) neurotoxicity presents an unmet medical need. Patients often report a cognitive decline in temporal correlation to chemotherapy, particularly for hippocampus-dependent verbal and visuo-spatial abilities. We treated adult C57Bl/6 mice with 12 × 20 mg kg(-1) paclitaxel (PTX), mimicking clinical conditions of dose-dense chemotherapy, followed by a pulse of bromodesoxyuridine (BrdU) to label dividing cells. In this model, mice developed visuo-spatial memory impairments, and we measured peak PTX concentrations in the hippocampus of 230 nm l(-1), which was sevenfold higher compared with the neocortex...
August 1, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28761134/the-neuroprotective-effect-of-hesperidin-in-nmda-induced-retinal-injury-acts-by-suppressing-oxidative-stress-and-excessive-calpain-activation
#8
Shigeto Maekawa, Kota Sato, Kosuke Fujita, Reiko Daigaku, Hiroshi Tawarayama, Namie Murayama, Satoru Moritoh, Takeshi Yabana, Yukihiro Shiga, Kazuko Omodaka, Kazuichi Maruyama, Koji M Nishiguchi, Toru Nakazawa
We found that hesperidin, a plant-derived bioflavonoid, may be a candidate agent for neuroprotective treatment in the retina, after screening 41 materials for anti-oxidative properties in a primary retinal cell culture under oxidative stress. We found that the intravitreal injection of hesperidin in mice prevented reductions in markers of the retinal ganglion cells (RGCs) and RGC death after N-methyl-D-aspartate (NMDA)-induced excitotoxicity. Hesperidin treatment also reduced calpain activation, reactive oxygen species generation and TNF-α gene expression...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28760640/sialidase-neu3-defines-invasive-potential-of-human-glioblastoma-cells-by-regulating-calpain-mediated-proteolysis-of-focal-adhesion-proteins
#9
Kohta Takahashi, Sergei Proshin, Kazunori Yamaguchi, Yoji Yamashita, Ryuichi Katakura, Koji Yamamoto, Hiroshi Shima, Masahiro Hosono, Taeko Miyagi
BACKGROUND: Glioblastoma multiforme is one of the most malignant tumors of the human central nervous system characterized by high degree of invasiveness. Focusing on this invasive nature, we investigated whether ganglioside-specific sialidase NEU3 might be involved, because gangliosides are major components of brain tissues, and cell surface sialic acids, as target residues of sialidase catalysis, are thought to be closely related to cell invasion. METHODS: NEU3 mRNA levels of human glioblastoma specimens were evaluated by quantitative RT-PCR...
July 29, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28760262/corrigendum-to-disruption-of-calpain-reduces-lipotoxicity-induced-cardiac-injury-by-preventing-endoplasmic-reticulum-stress-biochim-biophy-acta-1862-11-2023-2033
#10
S Li, L Zhang, R Ni, T Cao, D Zheng, S Xiong, P A Greer, G C Fan, T Peng
No abstract text is available yet for this article.
September 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28759231/discovery-of-novel-and-highly-selective-inhibitors-of-calpain-for-the-treatment-of-alzheimer%C3%A2-s-disease-2-3-phenyl-1h-pyrazol-1-yl-nicotinamides
#11
Andreas Kling, Katja Jantos, Helmut Mack, Wilfried Hornberger, Karla Drescher, Volker Nimmrich, Ana Relo, Karsten Wicke, Charles W Hutchins, Yanbin Lao, Kennan C Marsh, Achim Moeller
Calpain overactivation has been implicated in a variety of pathological disorders including ischemia/reperfusion injury, cataract formation, and neurodegenerative diseases such as Alzheimer´s Disease (AD). Herein we describe our efforts leading to the identification of ketoamide-based 2-(3-phenyl-1H-pyrazol-1-yl)nicotinamides as potent and reversible inhibitors of calpain with high selectivity versus related cysteine protease cathepsins, other proteases and receptors. Broad efficacy in a set of preclinical models relevant to AD suggests that inhibition of calpain represents an attractive approach with potential benefit for the treatment of AD...
July 31, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28758430/calpain-inhibitor-attenuates-atherosclerosis-and-inflammation-in-atherosclerotic-rats-through-enos-no-nf-%C3%AE%C2%BAb-pathway
#12
Lan Yu, Meihui Yin, Xueyan Yang, Meili Lu, Futian Tang, Hongxin Wang
We previously reported that calpain, the Ca2+-sensitive cysteine protease, gets involved in the atherogenesis. This study was to investigate the effects of calpain inhibitor (CAI, 5 mg/kg/d) with or without NG-nitro-L-arginine-methyl ester (L-NAME) (100 mg/kg/d), the inhibitor of nitric oxide synthase (NOS), on atherosclerosis and inflammation in rat model induced by high cholesterol diet (HCD). The results demonstrated HCD increased protein expression of calpain-1 but not calpain-2 in aortic tissue. In addition, CAI reduced the thickness of atherosclerotic intima compared to HCD group, which was weakened by the L-NAME combination...
July 30, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28754591/camkii-inhibition-mitigates-ischemia-reperfusion-elicited-calpain-activation-and-the-damage-to-membrane-skeleton-proteins-in-isolated-rat-hearts
#13
Ling-Heng Kong, Xiao-Ming Gu, Feng Wu, Zhen-Xiao Jin, Jing-Jun Zhou
Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) has been implicated in myocardial ischemia/reperfusion (IR) injury. The aim of this study was to determine the effect of CaMKII on the damage to membrane skeleton proteins, which is an important cause of IR injury. Isolated rat hearts were subjected to 45-min global ischemia/2-h reperfusion. Both KN-62 and KN-93 were used to inhibit CaMKII. Compared with controls, the hearts in the IR group exhibited remarkable myocardial injury area, LDH release, cell apoptosis and contractile dysfunction, along with an increase in the phosphorylation of CaMKII and its substrate phospholamban...
July 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28749416/anti-oxidative-stress-activity-is-essential-for-amanita-caesarea-mediated-neuroprotection-on-glutamate-induced-apoptotic-ht22-cells-and-an-alzheimer-s-disease-mouse-model
#14
Zhiping Li, Xia Chen, Wenqian Lu, Shun Zhang, Xin Guan, Zeyu Li, Di Wang
Amanita caesarea, an edible mushroom found mainly in Asia and southern Europe, has been reported to show good antioxidative activities. In the present study, the neuroprotective effects of A. caesarea aqueous extract (AC) were determined in an l-glutamic acid (l-Glu) induced HT22 cell apoptosis model, and in a d-galactose (d-gal) and AlCl₃-developed experimental Alzheimer's disease (AD) mouse model. In 25 mM of l-Glu-damaged HT22 cells, a 3-h pretreatment with AC strongly improved cell viability, reduced the proportion of apoptotic cells, restored mitochondrial function, inhibited the over-production of intracellular reactive oxygen species (ROS) and Ca(2+), and suppressed the high expression levels of cleaved-caspase-3, calpain 1, apoptosis-inducing factor (AIF) and Bax...
July 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28746873/deletion-of-glut1-and-glut3-reveals-multiple-roles-for-glucose-metabolism-in-platelet-and-megakaryocyte-function
#15
Trevor P Fidler, Robert A Campbell, Trevor Funari, Nicholas Dunne, Enrique Balderas Angeles, Elizabeth A Middleton, Dipayan Chaudhuri, Andrew S Weyrch, E Dale Abel
Anucleate platelets circulate in the blood to facilitate thrombosis and diverse immune functions. Platelet activation leading to clot formation correlates with increased glycogenolysis, glucose uptake, glucose oxidation, and lactic acid production. Simultaneous deletion of glucose transporter (GLUT) 1 and GLUT3 (double knockout [DKO]) specifically in platelets completely abolished glucose uptake. In DKO platelets, mitochondrial oxidative metabolism of non-glycolytic substrates, such as glutamate, increased...
July 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28743718/twinfilin-2a-is-a-regulator-of-platelet-reactivity-and-turnover-in-mice
#16
Simon Stritt, Sarah Beck, Isabelle C Becker, Timo Vögtle, Markku Hakala, Katrin G Heinze, Xiaoping Du, Markus Bender, Attila Braun, Pekka Lappalainen, Bernhard Nieswandt
Regulated reorganization of the actin cytoskeleton is a prerequisite for proper platelet production and function. Consequently, defects in proteins controlling actin dynamics have been associated with platelet disorders in humans and mice. Twinfilin 2a (Twf2a) is a small actin-binding protein, which inhibits actin filament assembly by sequestering actin monomers and by capping filament barbed ends. Moreover, Twf2a binds heterodimeric capping proteins, but the role of this interaction in cytoskeletal dynamics has remained elusive...
July 25, 2017: Blood
https://www.readbyqxmd.com/read/28727083/influence-of-feed-efficiency-classification-and-growing-and-finishing-diet-type-on-meat-tenderness-attributes-of-beef-steers
#17
C P Blank, J Russell, S M Lonergan, S L Hansen
Enhancing feed efficiency (FE) in cattle continues to be an important goal in the beef industry. Previous research suggests improving FE may alter calpain system activity, potentially having negative effects on meat tenderness. The objective of this study was to assess the potential influence of beef cattle FE on postmortem meat tenderness. During the growing phase, 181 crossbred steers were fed for 76 d at the University of Missouri on a whole shell corn-based diet (MU-Corn; = 90) or a roughage-based diet (MU-Rough; = 91)...
July 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28719590/pericyte-expressed-tie2-controls-angiogenesis-and-vessel-maturation
#18
Martin Teichert, Laura Milde, Annegret Holm, Laura Stanicek, Nicolas Gengenbacher, Soniya Savant, Tina Ruckdeschel, Zulfiyya Hasanov, Kshitij Srivastava, Junhao Hu, Stella Hertel, Arne Bartol, Katharina Schlereth, Hellmut G Augustin
The Tie receptors with their Angiopoietin ligands act as regulators of angiogenesis and vessel maturation. Tie2 exerts its functions through its supposed endothelial-specific expression. Yet, Tie2 is also expressed at lower levels by pericytes and it has not been unravelled through which mechanisms pericyte Angiopoietin/Tie signalling affects angiogenesis. Here we show that human and murine pericytes express functional Tie2 receptor. Silencing of Tie2 in pericytes results in a pro-migratory phenotype. Pericyte Tie2 controls sprouting angiogenesis in in vitro sprouting and in vivo spheroid assays...
July 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28718687/do-sodium-channel-proteolytic-fragments-regulate-sodium-channel-expression
#19
Donatus O Onwuli, Laia Yañez-Bisbe, Mel Lina Pinsach-Abuin, Anna Tarradas, Ramon Brugada, John Greenman, Sara Pagans, Pedro Beltran-Alvarez
The cardiac voltage-gated sodium channel (gene: SCN5A, protein: NaV1.5) is responsible for the sodium current that initiates the cardiomyocyte action potential. Research into the mechanisms of SCN5A gene expression has gained momentum over the last few years. We have recently described the transcriptional regulation of SCN5A by GATA4 transcription factor. In this addendum to our study, we report our observations that 1) the linker between domains I and II (LDI-DII) of NaV1.5 contains a nuclear localization signal (residues 474-481) that is necessary to localize LDI-DII into the nucleus, and 2) nuclear LDI-DII activates the SCN5A promoter in gene reporter assays using cardiac-like H9c2 cells...
July 18, 2017: Channels
https://www.readbyqxmd.com/read/28717166/targeting-cellular-calcium-homeostasis-to-prevent-cytokine-mediated-beta-cell-death
#20
Amy L Clark, Kohsuke Kanekura, Zeno Lavagnino, Larry D Spears, Damien Abreu, Jana Mahadevan, Takuya Yagi, Clay F Semenkovich, David W Piston, Fumihiko Urano
Pro-inflammatory cytokines are important mediators of islet inflammation, leading to beta cell death in type 1 diabetes. Although alterations in both endoplasmic reticulum (ER) and cytosolic free calcium levels are known to play a role in cytokine-mediated beta cell death, there are currently no treatments targeting cellular calcium homeostasis to combat type 1 diabetes. Here we show that modulation of cellular calcium homeostasis can mitigate cytokine- and ER stress-mediated beta cell death. The calcium modulating compounds, dantrolene and sitagliptin, both prevent cytokine and ER stress-induced activation of the pro-apoptotic calcium-dependent enzyme, calpain, and partly suppress beta cell death in INS1E cells and human primary islets...
July 17, 2017: Scientific Reports
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