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Calpain

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https://www.readbyqxmd.com/read/28640887/epidermal-growth-factor-promotes-cyclin-g2-degradation-via-calpain-mediated-proteolysis-in-gynaecological-cancer-cells
#1
Stefanie Bernaudo, Shahin Khazai, Eilyad Honarparvar, Alina Kopteva, Chun Peng
Cyclin G2 (CCNG2) is an atypical cyclin that functions to inhibit cell cycle progression and is often dysregulated in human cancers. We have previously shown that cyclin G2 is highly unstable and can be degraded through the ubiquitin/proteasome pathway. Furthermore, cyclin G2 contains a PEST domain, which has been suggested to act as a signal for degradation by multiple proteases. In this study, we determined if calpains, a family of calcium-dependent proteases, are also involved in cyclin G2 degradation. The addition of calpain inhibitors or silencing of calpain expression by siRNAs strongly enhanced cyclin G2 levels...
2017: PloS One
https://www.readbyqxmd.com/read/28630356/developmental-downregulation-of-lis1-expression-limits-axonal-extension-and-allows-axon-pruning
#2
Kanako Kumamoto, Tokuichi Iguchi, Ryuichi Ishida, Takuya Uemura, Makoto Sato, Shinji Hirotsune
The robust axonal growth and regenerative capacities of young neurons decrease substantially with age. This developmental downregulation of axonal growth may facilitate axonal pruning and neural circuit formation but limits functional recovery following nerve damage. While external factors influencing axonal growth have been extensively investigated, relatively little is known about the intrinsic molecular changes underlying the age-dependent reduction in regeneration capacity. We report that developmental downregulation of LIS1 is responsible for the decreased axonal extension capacity of mature dorsal root ganglion (DRG) neurons...
June 19, 2017: Biology Open
https://www.readbyqxmd.com/read/28630064/pneumolysin-dependent-calpain-activation-and-il-1%C3%AE-secretion-in-macrophages-infected-with-streptococcus-pneumoniae
#3
Rendong Fang, Rui Wu, Huihui Du, Meilan Jin, Yajing Liu, Guihua Lei, Bing Jiang, Zehui Lei, Yuanyi Peng, Kui Nie, Kohsuke Tsuchiya
Pneumolysin (PLY), a major virulence factor of Streptococcus pneumoniae, is a pore-forming cytolysin that modulates host innate responses contributing to host defense against and pathogenesis of pneumococcal infections. Interleukin-1α (IL-1α) has been shown to be involved in tissue damage in a pneumococcal pneumonia model, however, the mechanism by which this cytokine is produced during S. pneumoniae infection remains unclear. In this study, we examined the role of PLY in IL-1α production. Although the strains induced similar levels of pro-IL-1α expression, wild-type S...
June 19, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28625916/er-stress-disturbs-sr-er-mitochondria-ca-2-transfer-implications-in-duchenne-muscular-dystrophy
#4
Marion Pauly, Claire Angebault-Prouteau, Haikel Dridi, Cécile Notarnicola, Valérie Scheuermann, Alain Lacampagne, Stefan Matecki, Jérémy Fauconnier
Besides its role in calcium (Ca(2+)) homeostasis, the sarco-endoplamic reticulum (SR/ER) controls protein folding and is tethered to mitochondria.Under pathophysiological conditions the unfolded protein response (UPR) is associated with disturbance in SR/ER-mitochondria crosstalk. Here, we investigated whether ER stress altered SR/ER-mitochondria links, Ca(2+) handling and muscle damage in WT (Wild Type) and mdx mice, the murine model of Duchenne Muscular Dystrophy (DMD). In WT mice, the SR/ER-mitochondria links were decreased in isolated FDB muscle fibers after injection of ER stress activator tunicamycin (TM)...
June 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28623313/inhibition-of-calpains-protects-mn-induced-neurotransmitter-release-disorders-in-synaptosomes-from-mice-involvement-of-snare-complex-and-synaptic-vesicle-fusion
#5
Can Wang, Bin Xu, Zhuo Ma, Chang Liu, Yu Deng, Wei Liu, Zhao-Fa Xu
Overexposure to manganese (Mn) could disrupt neurotransmitter release via influencing the formation of SNARE complex, but the underlying mechanisms are still unclear. A previous study demonstrated that SNAP-25 is one of substrate of calpains. The current study investigated whether calpains were involved in Mn-induced disorder of SNARE complex. After mice were treated with Mn for 24 days, Mn deposition increased significantly in basal nuclei in Mn-treated and calpeptin pre-treated groups. Behaviorally, less time spent in the center of the area and decreased average velocity significantly in an open field test after 24 days of Mn exposure...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28623080/increased-constitutive-nitric-oxide-production-by-whole-body-periodic-acceleration-ameliorates-alterations-in-cardiomyocytes-associated-with-utrophin-dystrophin-deficiency
#6
Jose R Lopez, Juan Kolster, Rui Zhang, Jose Adams
Duchenne Muscular Dystrophy (DMD) cardiomyopathy is a progressive lethal disease caused by the lack of the dystrophin protein in the heart. The most widely used animal model of DMD is the dystrophin-deficient mdx mouse; however, these mice exhibit a mild dystrophic phenotype with heart failure only late in life. In contrast, mice deficient for both dystrophin and utrophin (mdx/utrn(-/-), or dKO) can be used to model severe DMD cardiomyopathy where pathophysiological indicators of heart failure are detectable by 8-10weeks of age...
June 13, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28616018/collapsin-response-mediator-protein-2-plays-a-major-protective-role-in-acute-axonal-degeneration
#7
REVIEW
Jian-Nan Zhang, Jan C Koch
Axonal degeneration is a key pathological feature in many neurological diseases. It often leads to persistent deficits due to the inability of axons to regenerate in the central nervous system. Therefore therapeutic approaches should optimally both attenuate axonal degeneration and foster axonal regeneration. Compelling evidence suggests that collapsin response mediator protein-2 (CRMP2) might be a molecular target fulfilling these requirements. In this mini-review, we give a compact overview of the known functions of CRMP2 and its molecular interactors in neurite outgrowth and in neurodegenerative conditions...
May 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28608220/calpain-zymography-general-methodology-and-protocol
#8
Kevin K W Wang
Casein zymography has become one of the gold standard assays for monitoring mammalian calcium-activated proteases (calpains) in purified enzyme, cell, or tissue samples. This calpain zymography method takes advantages of (1) casein is an excellent substrate for major isoforms of calpains (Calpain-1, 2 and 3), (2) the embedded casein is digested into small peptides where the calpain bands are located, thus creating a clear zone upon Commassie blue gel staining, and (3) the calpain isoforms have different gel mobility under native gel conditions...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28602176/calpainopathy-with-macrophage-rich-regional-inflammatory-infiltrates
#9
Peter W Schutz, Renata S Scalco, Rita Barresi, Henry Houlden, Matthew Parton, Janice L Holton
Mutations in calpain-3 cause limb girdle muscular dystrophy 2A. Biopsy pathology is typically dystrophic, sometimes characterized by frequent lobulated fibres. More recently calpain mutations have been shown in association with eosinophilic myositis, suggesting that calpain mutations may render muscle susceptible to inflammatory change. We present the case of a 33-year old female with mild proximal muscle weakness and high CK levels (6698 IU/L at presentation). Muscle biopsy showed clusters of fibre necrosis associated with very dense macrophage infiltrates and small numbers of lymphocytes, raising the possibility of an inflammatory myopathy...
April 27, 2017: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/28596571/the-role-of-trpc6-in-the-neuroprotection-of-calycosin-against-cerebral-ischemic-injury
#10
Chao Guo, Yongyuan Ma, Shanbo Ma, Fei Mu, Jiao Deng, Jialin Duan, Lize Xiong, Ying Yin, Yanhua Wang, Miaomaio Xi, Aidong Wen
Our previous studies have provided evidences that calycosin can protect the brain from ischemia/reperfusion injury, but its mechanisms is not fully understand. Transient receptor potential canonical 6 (TRPC6) has a critical role in promoting neuronal survival against cerebral ischemic injury. The aim of the present study is to test whether calycosin protects against cerebral ischemic injury through TRPC6-CREB pathway. In vivo, rats were subjected to transient middle cerebral artery occlusion (MCAO) for 2 h and then treated with different doses of calycosin at the onset of reperfusion...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28595796/the-metal-and-metalloprotein-profile-of-human-plasma-as-biomarkers-for-stroke-diagnosis
#11
Keaton S Nahan, Kyle B Walsh, Opeolu Adeoye, Julio A Landero-Figueroa
Stroke, a major cause of disability and mortality, affects someone in the United States every 40s. Stroke biomarkers, including those that could be used as a blood test for diagnosis of stroke, have been particularly elusive. We performed a double blind study to identify human plasma biomarkers for the diagnosis of stroke, including acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH). We utilized a three-track approach based on the total metal profile, the metal cofactor levels among metalloproteins, and the identification of stroke-related metalloproteins...
July 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/28595650/acute-neuroinflammation-induces-ais-structural-plasticity-in-a-nox2-dependent-manner
#12
S D Benusa, N M George, B A Sword, G H DeVries, J L Dupree
BACKGROUND: Chronic microglia-mediated inflammation and oxidative stress are well-characterized underlying factors in neurodegenerative disease, whereby reactive inflammatory microglia enhance ROS production and impact neuronal integrity. Recently, it has been shown that during chronic inflammation, neuronal integrity is compromised through targeted disruption of the axon initial segment (AIS), the axonal domain critical for action potential initiation. AIS disruption was associated with contact by reactive inflammatory microglia which wrap around the AIS, increasing association with disease progression...
June 8, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28594313/protection-against-tbi-induced-neuronal-death-with-post-treatment-with-a-selective-calpain-2-inhibitor-in-mice
#13
Yubin Wang, Yan Liu, Dulce Lopez, Moses Lee, Sujay Dayal, Alexander Hurtado, Xiaoning Bi, Michel Baudry
Traumatic Brain Injury (TBI) is a major cause of death and disability worldwide. The calcium-dependent protease, calpain, has been shown to be involved in TBI-induced neurodegenerationneuronal death. However, while various calpain inhibitors have been tested in several animal models of TBI, there has not been any clinical trial testing the efficacy of calpain inhibitors in human TBI. One important reason for this could be the lack of knowledge regarding the differential functions of the two major calpain isoforms in the brain, calpain-1 and calpain-2...
June 8, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28588694/high-level-of-calpain1-promotes-cancer-cell-invasion-and-migration-in-oral-squamous-cell-carcinoma
#14
Da Ma, Juan Fang, Ying Liu, Jing-Jing Song, Yan-Qiong Wang, Juan Xia, Bin Cheng, Zhi Wang
Calpain1, termed conventional calpain and a member of the Ca(2+)-dependent neutral cysteine proteases, is considered to be involved in cancer formation and development. However, the effect of calpain1 on oral squamous cell carcinoma (OSCC) remains poorly understood. The aim of the present study was to evaluate the possibility of calpain1 as a potential molecular target for OSCC diagnosis and therapy. The present study demonstrates that calpain1 was overexpressed in OSCC cell lines and 4/7 of the tumor tissues in paired samples of tumor and noncancerous matched tissues (NCMT)...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28579809/mir-124-suppresses-proliferation-and-invasion-of-nasopharyngeal-carcinoma-cells-through-the-wnt-%C3%AE-catenin-signaling-pathway-by-targeting-capn4
#15
Haili Hu, Guanghui Wang, Congying Li
BACKGROUND: Recent studies have demonstrated that microRNA 124 (miR-124) acts as a tumor suppressor in nasopharyngeal carcinoma (NPC); however, the exact molecular mechanism by which miR-124 exerts tumor suppression has not been well elucidated. MATERIALS AND METHODS: We performed quantitative real-time PCR (qRT-PCR) to measure the expression of metastasis associated lung adenocarcinoma transcript 1, miR-124, and calpain small subunit 1 (Capn4) mRNAs in NPC cell lines...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28579451/the-fifth-sense-mechanosensory-regulation-of-alpha-actinin-4-and-its-relevance-for-cancer-metastasis
#16
REVIEW
Dustin G Thomas, Douglas N Robinson
Metastatic cancer cells invading through dense tumor stroma experience internal and external forces that are sensed through a variety of mechanosensory proteins that drive adaptations for specific environments. Alpha-actinin-4 (ACTN4) is a member of the α-actinin family of actin crosslinking proteins that is upregulated in several types of cancers. It shares 86% protein similarity with α-actinin-1, another non-muscle ACTN isoform, which appears to have a more modest role, if any, in cancer progression. While they share regulatory mechanisms, such as phosphorylation, calcium binding, phosphatidyl inositol binding, and calpain cleavage, α-actinin-4 exhibits a unique mechanosensory regulation that α-actinin-1 does not...
June 1, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28562483/investigation-of-the-expression-of-apoptosis-inducing-factor-mediated-apoptosis-in-hirschsprung-s-disease
#17
Xin Ge, Chunyan Hu, Qingqing Guo, Wei Li, Yuying Zhao, Weili Yang, Yudu Wang, Peng Li, Ya Gao, Qiang Huang
One of the widely accepted hypotheses of Hirschsprung's disease (HD) is that the absence of ganglion cells in the distal part of the intestine is caused by the death of enteric neural crest-derived cells following migration. Although a caspase-dependent pathway has not yet been detected in the HD bowel, it is unclear whether a caspase-independent pathway contributes toward aganglionosis. In the current study, we observed highly condensed marginal heterochromatin in nuclei only in the transitional segment using electron microscopy and a high proportion of TUNEL-positive cells were observed in the transitional segment...
July 5, 2017: Neuroreport
https://www.readbyqxmd.com/read/28559121/calpain-2-p35-p25-cdk5-pathway-is-involved-in-the-neuronal-apoptosis-induced-by-polybrominated-diphenyl-ether-153
#18
Hongmei Zhang, Lijun Chang, Huajun Zhang, Jisheng Nie, Zhihong Zhang, Xiaorong Yang, Ann M Vuong, Zemin Wang, Aimin Chen, Qiao Niu
Polybrominated diphenyl ethers (PBDEs) have been demonstrated to induce neurotoxicity in experimental rats and mice, with neuronal apoptosis as one of the major mechanisms, however, the mechanisms underlying PBDEs-induced neuronal apoptosis remain unclear. In this study, we aimed to investigate the role of calpain/p35-p25/Cdk5 pathway in BDE-153-induced neuronal apoptosis in the hippocampus and primary neurons in rats. Results showed that compared to the controls, neuronal apoptosis was significantly increased in vivo and ex vivo, as manifested by the increased hippocampus TUNEL-positive cell rates, apoptotic neurons in Hoechst and AO/EB staining, and the increased LDH activity and percentage of Annexin V-positive cells in rat hippocampus and primary neurons...
May 27, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28553344/ca-2-involvement-in-activation-of-extracellular-signal-regulated-kinase-1-2-and-m-calpain-after-axotomy-of-the-sciatic-nerve
#19
Lisa B Mårtensson, Charlotta Lindwall Blom, Lars B Dahlin
Detailed mechanisms behind regeneration after nerve injury, in particular signal transduction and the fate of Schwann cells (SCs), are poorly understood. Here, we investigated axotomy-induced activation of extracellular-signal-regulated kinase-1/2 (ERK1/2; important for proliferation) and m-calpain in vitro, and the relation to Ca(2+) deletion and Schwann cell proliferation and death after rat sciatic nerve axotomy. Nerve segments were cultured for up to 72 hours with and without ethylene glycol-bis(β-aminoethyl ether)-N, N, N', N'-tetraacetic acid (EGTA)...
April 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28542880/suicidal-death-of-erythrocytes-in-cancer-and-its-chemotherapy-a-potential-target-in-the-treatment-of-tumor-associated-anemia
#20
REVIEW
Elisabeth Lang, Rosi Bissinger, Syed M Qadri, Florian Lang
In analogy to apoptosis of nucleated cells, erythrocytes may enter eryptosis characterized by cell shrinkage and cell membrane scrambling. Eryptotic erythrocytes are rapidly cleared from circulating blood and may adhere to the vascular wall. Stimulation of eryptosis thus impairs microcirculation and leads to anemia as soon as the loss of erythrocytes cannot be fully compensated by enhanced erythropoiesis. Signaling stimulating eryptosis includes increase of cytosolic Ca(2+) -activity, ceramide, caspases, calpain, p38-kinase, protein-kinase C, Janus-activated kinase 3, casein-kinase 1α, and cyclin-dependent kinase 4...
May 23, 2017: International Journal of Cancer. Journal International du Cancer
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