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Calpastatin

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https://www.readbyqxmd.com/read/27875293/attenuation-of-blood-brain-barrier-breakdown-and-hyperpermeability-by-calpain-inhibition
#1
Himakarnika Alluri, Marcene Grimsley, Chinchusha Anasooya Shaji, Kevin Paul Varghese, Shenyuan L Zhang, Chander Peddaboina, Bobby Robinson, Madhava R Beeram, Jason H Huang, Binu Tharakan
Blood-brain barrier (BBB) breakdown and the associated microvascular hyperpermeability followed by brain edema is a hallmark feature of several brain pathologies including traumatic brain injuries (TBI). Recent studies indicate that pro-inflammatory cytokine interleukin-1β (IL-1β) that is upregulated following traumatic injuries also promotes BBB dysfunction and hyperpermeability but the underlying mechanisms are not clearly known. The objective of this study was to determine the role of calpains in mediating BBB dysfunction and hyperpermeability and to test the effect of calpain inhibition on the BBB following traumatic insults to the brain...
November 8, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27835610/roles-of-calpain-calpastatin-system-ccs-in-human-t-cell-activation
#2
Anna Mikosik, Aleksandra Jasiulewicz, Agnieszka Daca, Izabella Henc, Joanna E Frąckowiak, Katarzyna Ruckemann-Dziurdzińska, Jerzy Foerster, Aurelie Le Page, Ewa Bryl, Tamas Fulop, Jacek M Witkowski
The immune response is determined by the speed of the T cell reaction to antigens assured by a state of readiness for proliferation and cytokine secretion. Proliferation, apoptosis and motion of many cell types are controlled by cytoplasmic proteases - µ- and m-calpain - and their inhibitor calpastatin, together forming the "calpain-calpastatin system" (CCS), assumed to modify their targets only upon activation-dependent cytoplasmic Ca2+ increase. Contrastingly to this notion, using quantitative real time PCR and semiquantitative flow cytometry respectively, we show here that the CCS genes are constitutively expressed, and that both calpains are constitutively active in resting, circulating human CD4+ and CD8+ lymphocytes...
November 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27812546/%C3%AE-cell-specific-increased-expression-of-calpastatin-prevents-diabetes-induced-by-islet-amyloid-polypeptide-toxicity
#3
Tatyana Gurlo, Safia Costes, Jonathan D Hoang, Jacqueline F Rivera, Alexandra E Butler, Peter C Butler
The islet in type 2 diabetes (T2D) shares many features of the brain in protein misfolding diseases. There is a deficit of β cells with islet amyloid derived from islet amyloid polypeptide (IAPP), a protein coexpressed with insulin. Small intracellular membrane-permeant oligomers, the most toxic form of IAPP, are more frequent in β cells of patients with T2D and rodents expressing human IAPP. β Cells in T2D, and affected cells in neurodegenerative diseases, share a comparable pattern of molecular pathology, including endoplasmic reticulum stress, mitochondrial dysfunction, attenuation of autophagy, and calpain hyperactivation...
November 3, 2016: JCI Insight
https://www.readbyqxmd.com/read/27765842/adrenodemedullation-activates-the-ca2-dependent-proteolysis-in-soleus-muscles-from-rats-exposed-to-cold
#4
Leandro H Manfredi, D Lustrino, Juliano Machado, Wilian Assis Silveira, Neusa Maria Zanon, Luiz C Navegantes, Isis do Carmo Kettelhut
Previous studies have shown that catecholamines in vivo and in vitro inhibit the activity of Ca(2+)-dependent proteolysis in skeletal muscles under basal conditions. In the present study we sought to investigate the role of catecholamines in regulating the Ca(2+)-dependent proteolysis in soleus and extensor digitorum longus (EDL) muscles from rats acutely exposed to cold. Overall proteolysis, the activity of proteolytic systems as well as protein levels and gene expression of different components of calpain system were investigated in rats submitted to adrenodemedullation (ADMX) and exposed to cold for 24 h...
October 20, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27747292/role-of-calpain-in-pathogenesis-of-human-disease-processes
#5
Brittany A Potz, M Ruhul Abid, Frank W Sellke
Calpains are a 15-member class of calcium activated nonlysosomal neutral proteases which are involved in a broad range of cellular function. Calpains are usually localized to the cytosol and within mitochondria. Calpastatin is an endogenous protein that specifically binds to and inhibits calpain. Overactivation of calpain has been implicated in a number of disease processes of the brain, eyes, heart, lungs, pancreas, kidneys, vascular system and skeletal muscle. Therefore, calpain may serve as a potential therapeutic target for a wide variety of disease processes...
2016: Journal of Nature and Science
https://www.readbyqxmd.com/read/27715410/kshv-reduces-autophagy-in-thp-1-cells-and-in-differentiating-monocytes-by-decreasing-cast-calpastatin-and-atg5-expression
#6
R Santarelli, M Granato, G Pentassuglia, V Lacconi, M S Gilardini Montani, R Gonnella, M Tafani, M R Torrisi, A Faggioni, M Cirone
We have previously shown that Kaposi sarcoma-associated herpesvirus (KSHV) impairs monocyte differentiation into dendritic cells (DCs). Macroautophagy/autophagy has been reported to be essential in such a differentiating process. Here we extended these studies and found that the impairment of DC formation by KSHV occurs through autophagy inhibition. KSHV indeed reduces CAST (calpastatin) and consequently decreases ATG5 expression in both THP-1 monocytoid cells and primary monocytes. We unveiled a new mechanism put in place by KSHV to escape from immune control...
October 7, 2016: Autophagy
https://www.readbyqxmd.com/read/27635352/effect-of-8-hydroxyquinoline-and-derivatives-on-human-neuroblastoma-sh-sy5y-cells-under-high-glucose
#7
Wilasinee Suwanjang, Supaluk Prachayasittikul, Virapong Prachayasittikul
8-Hydroxyquinoline and derivatives exhibit multifunctional properties, including antioxidant, antineurodegenerative, anticancer, anti-inflammatory and antidiabetic activities. In biological systems, elevation of intracellular calcium can cause calpain activation, leading to cell death. Here, the effect of 8-hydroxyquinoline and derivatives (5-chloro-7-iodo-8-hydroxyquinoline or clioquinol and 8-hydroxy-5-nitroquinoline or nitroxoline) on calpain-dependent (calpain-calpastatin) pathways in human neuroblastoma (SH-SY5Y) cells was investigated...
2016: PeerJ
https://www.readbyqxmd.com/read/27472894/dual-roles-of-calpain-in-facilitating-coxsackievirus-b3-replication-and-prompting-inflammation-in-acute-myocarditis
#8
Minghui Li, Yangang Su, Yong Yu, Ying Yu, Xinggang Wang, Yunzeng Zou, Junbo Ge, Ruizhen Chen
BACKGROUND: Viral myocarditis (VMC) treatment has long been lacking of effective methods. Our former studies indicated roles of calpain in VMC pathogenesis. This study aimed at verifying the potential of calpain in Coxsackievirus B3 (CVB3)-induced myocarditis treatment. METHODS: A transgenic mouse overexpressing the endogenous calpain inhibitor, calpastatin, was introduced in the study. VMC mouse model was established via intraperitoneal injection of CVB3 in transgenic and wild mouse respectively...
October 15, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27456359/gene-protein-expression-of-capn1-2-cast-system-members-is-associated-with-erk1-2-kinases-activity-as-well-as-progression-and-clinical-outcome-in-human-laryngeal-cancer
#9
Katarzyna Starska, Ewa Forma, Paweł Jóźwiak, Iwona Lewy-Trenda, Marian Danilewicz, Olga Stasikowska-Kanicka, Michał Skóra, Katarzyna Kolary, Jakub Miazga, Anna Krześlak, Magdalena Bryś
Recent evidence indicates the involvement of calpains (CAPNs), a family of cysteine proteases, in cancer development and progression, as well as the insufficient response to cancer therapies. The contribution of CAPNs and regulatory calpastatin (CAST) and ERK1/2 kinases to aggressiveness, disease course, and outcome in laryngeal cancer remains elusive. This study was aimed to evaluate the CAPN1/2-CAST-ERK1/2 enzyme system mRNA/protein level and to investigate whether they can promote the dynamic of tumor growth and prognosis...
July 25, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27453531/the-inhibition-of-calpains-ameliorates-vascular-restenosis-through-mmp2-tgf-%C3%AE-1-pathway
#10
Lianghu Tang, Haifeng Pei, Yi Yang, Xiong Wang, Ting Wang, Erhe Gao, De Li, Yongjian Yang, Dachun Yang
Restenosis limits the efficacy of vascular percutaneous intervention, in which vascular smooth muscle cell (VSMC) proliferation and activation of inflammation are two primary causal factors. Calpains influence VSMC proliferation and collagen synthesis. However, the roles of calpastatin and calpains in vascular restenosis remain unclear. Here, restenosis was induced by ligating the left carotid artery, and VSMCs were pretreated with platelet-derived growth factor (PDGF)-BB. Adenovirus vector carrying MMP2 sequence and specific small interfering RNA against calpain-1/2 were introduced...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27453331/calpastatin-overexpression-reduces-oxidative-stress-induced-mitochondrial-impairment-and-cell-death-in-human-neuroblastoma-sh-sy5y-cells-by-decreasing-calpain-and-calcineurin-activation-induction-of-mitochondrial-fission-and-destruction-of-mitochondrial-fusion
#11
Kulvadee Tangmansakulchai, Zuroida Abubakar, Narisorn Kitiyanant, Wilasinee Suwanjang, Chaniya Leepiyasakulchai, Piyarat Govitrapong, Banthit Chetsawang
Calpain is an intracellular Ca(2+)-dependent protease, and the activation of calpain has been implicated in neurodegenerative diseases. Calpain activity can be regulated by calpastatin, an endogenous specific calpain inhibitor. Several lines of evidence have demonstrated a potential role of calpastatin in preventing calpain-mediated pathogenesis. Additionally, several studies have revealed that calpain activation and mitochondrial damage are involved in the cell death process; however, recent evidence has not clearly indicated a neuroprotective mechanism of calpastatin against calpain-dependent mitochondrial impairment in the process of neuronal cell death...
September 2016: Mitochondrion
https://www.readbyqxmd.com/read/27427783/zilpaterol-hydrochloride-improves-beef-yield-changes-palatability-traits-and-increases-calpain-calpastatin-gene-expression-in-nellore-heifers
#12
Nara Regina Brandão Cônsolo, Viviane Borba Ferrari, Ligia Garcia Mesquita, Rodrigo Silva Goulart, Luis Felipe Prada E Silva
This research aimed to evaluate the effects of the beta-agonist zilpaterol hydrochloride (ZH) on carcass traits, subprimal yield, meat quality, palatability traits, and gene expression in Nellore heifers. Zilpaterol increased Longissimus lumborum area and did not change back fat thickness, meat color, and cooking loss. Heifers fed ZH had greater hindquarter weight and carcass percentage. Muscles from hindquarter were heavier for animals fed ZH. Forequarter (% of carcass) decreased and brisket did not change with ZH supplementation...
November 2016: Meat Science
https://www.readbyqxmd.com/read/27420951/single-nucleotide-polymorphisms-associated-with-carcass-traits-in-a-population-of-brahman-and-brahman-influenced-steers
#13
A M Royer, C Shivers, D G Riley, M A Elzo, M D Garcia
Brahman cattle are important in tropical regions due to their ability to tolerate excessive heat and parasites. However, Brahman cattle exhibit lower carcass quality characteristics when compared to Bos taurus breeds. The objective of this study was to evaluate potential associations between single nucleotide polymorphisms (SNPs) in six candidate genes for carcass quality and composition traits in a population of Brahman and Brahman-influenced steers. Steers were evaluated through the American Brahman Breeders Association carcass evaluation project in Gonzales, Texas...
2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27323818/the-calpain-system-is-associated-with-survival-of-breast-cancer-patients-with-large-but-operable-inflammatory-and-non-inflammatory-tumours-treated-with-neoadjuvant-chemotherapy
#14
Sarah J Storr, Siwei Zhang, Tim Perren, Mark Lansdown, Hiba Fatayer, Nisha Sharma, Renu Gahlaut, Abeer Shaaban, Stewart G Martin
The calpains are a family of intracellular cysteine proteases that function in a variety of important cellular functions, including cell signalling, motility, apoptosis and survival. In early invasive breast cancer expression of calpain-1, calpain-2 and their inhibitor, calpastatin, have been associated with clinical outcome and clinicopathological factors.The expression of calpain-1, calpain-2 and calpastatin was determined using immunohistochemistry on core biopsy samples, in a cohort of large but operable inflammatory and non-inflammatory primary breast cancer patients treated with neoadjuvant chemotherapy...
June 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27294874/a-calcium-and-calpain-dependent-pathway-determines-the-response-to-lenalidomide-in-myelodysplastic-syndromes
#15
Jing Fang, Xiaona Liu, Lyndsey Bolanos, Brenden Barker, Carmela Rigolino, Agostino Cortelezzi, Esther N Oliva, Maria Cuzzola, H Leighton Grimes, Celia Fontanillo, Kakajan Komurov, Kyle MacBeth, Daniel T Starczynowski
Despite the high response rates of individuals with myelodysplastic syndrome (MDS) with deletion of chromosome 5q (del(5q)) to treatment with lenalidomide (LEN) and the recent identification of cereblon (CRBN) as the molecular target of LEN, the cellular mechanism by which LEN eliminates MDS clones remains elusive. Here we performed an RNA interference screen to delineate gene regulatory networks that mediate LEN responsiveness in an MDS cell line, MDSL. We identified GPR68, which encodes a G-protein-coupled receptor that has been implicated in calcium metabolism, as the top candidate gene for modulating sensitivity to LEN...
July 2016: Nature Medicine
https://www.readbyqxmd.com/read/27158675/eosinophilic-esophagitis-linked-calpain-14-is-an-il-13-induced-protease-that-mediates-esophageal-epithelial-barrier-impairment
#16
Benjamin P Davis, Emily M Stucke, M Eyad Khorki, Vladislav A Litosh, Jeffrey K Rymer, Mark Rochman, Jared Travers, Leah C Kottyan, Marc E Rothenberg
We recently identified a genome-wide genetic association of eosinophilic esophagitis (EoE) at 2p23 spanning the calpain 14 (CAPN14) gene, yet the causal mechanism has not been elucidated. We now show that recombinant CAPN14 cleaves a calpain-specific substrate and is inhibited by 4 classical calpain inhibitors: MDL-28170, acetyl-calpastatin, E-64, and PD151746. CAPN14 is specifically induced (>100-fold) in esophageal epithelium after IL-13 treatment. Epithelial cells overexpressing CAPN14 display impaired epithelial architecture, characterized by acantholysis, epidermal clefting, and epidermolysis...
April 2016: JCI Insight
https://www.readbyqxmd.com/read/27149983/dominant-and-recessive-mutations-in-rhodopsin-activate-different-cell-death-pathways
#17
Antonella Comitato, Maria Teresa Di Salvo, Giandomenico Turchiano, Monica Montanari, Sanae Sakami, Krzysztof Palczewski, Valeria Marigo
Mutations in rhodopsin (RHO) are a common cause of retinal dystrophy and can be transmitted by dominant or recessive inheritance. Clinical symptoms caused by dominant and recessive mutations in patients and animal models are very similar but the molecular mechanisms leading to retinal degeneration may differ. We characterized three murine models of retina degeneration caused by either Rho loss of function or expression of the P23H dominant mutation in Rho. Rho loss of function is characterized by activation of calpains and apoptosis-inducing factor (Aif) in dying photoreceptors...
May 5, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27148623/rational-design-of-calpain-inhibitors-based-on-calpastatin-peptidomimetics
#18
Kristin E Low, Spencer Ler, Kevin J Chen, Robert L Campbell, Jennifer L Hickey, Joanne Tan, Conor C G Scully, Peter L Davies, Andrei K Yudin, Serge Zaretsky
Our previously reported structures of calpain bound to its endogenous inhibitor calpastatin have motivated the use of aziridine aldehyde-mediated peptide macrocyclization toward the design of cyclic peptides and peptidomimetics as calpain inhibitors. Inspired by nature's hint that a β-turn loop within calpastatin forms a broad interaction around calpain's active site cysteine, we have constructed and tested a library of 45 peptidic compounds based on this loop sequence. Four molecules have shown reproducibly low micromolar inhibition of calpain-2...
June 9, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27121146/the-influence-of-maternal-nutrition-on-expression-of-genes-responsible-for-adipogenesis-and-myogenesis-in-the-bovine-fetus
#19
T D Jennings, M G Gonda, K R Underwood, A E Wertz-Lutz, A D Blair
The objective of this study was to determine whether altered maternal energy supply during mid-gestation results in differences in muscle histology or genes regulating fetal adipose and muscle development. In total, 22 Angus cross-bred heifers (BW=527.73±8.3 kg) were assigned randomly to the three dietary treatments providing 146% (HIGH; n=7), 87% (INT; n=7) or 72% (LOW; n=8) of the energy requirements for heifers from day 85 to day 180 of gestation. Fetuses were removed via cesarean section at day 180 of gestation and longissimus muscle (LM) and subcutaneous fat were collected and prepared for analysis of gene expression...
October 2016: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/27119554/protective-effects-of-parp-inhibitor-pj34-is-related-to-down-regulation-of-calpain-and-nf-%C3%AE%C2%BAb-in-a-mouse-model-of-tbi
#20
Xiaogang Tao, Xuetao Chen, Xiang Mao, Zonggang Hou, Shuyu Hao, Runfa Tian, Zhendan Zhu, Ming Sun, Baiyun Liu
BACKGROUND: Poly(ADP-ribose) polymerase (PARP), calpain and nuclear factor-κB (NF-κB) are reported to participate in inflammatory reactions in pathological conditions and are involved in traumatic brain injury. The objective of this study was to investigate whether PARP participated in inflammation related to calpain and NF-κB in a mouse model of controlled cortical impact (CCI). MATERIALS AND METHODS: PJ34 (10 mg kg(-1)), a selective PARP inhibitor, was administered intraperitoneally 5 minutes and 8 hours after experimental CCI...
April 27, 2016: Brain Injury: [BI]
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