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https://www.readbyqxmd.com/read/27925020/susceptibility-of-phytomonas-serpens-to-calpain-inhibitors-in-vitro-interference-on-the-proliferation-ultrastructure-cysteine-peptidase-expression-and-interaction-with-the-invertebrate-host
#1
Simone Santiago Carvalho de Oliveira, Diego de Souza Gonçalves, Aline Dos Santos Garcia-Gomes, Inês Correa Gonçalves, Sergio Henrique Seabra, Rubem Figueiredo Menna-Barreto, Angela Hampshire de Carvalho Santos Lopes, Claudia Masini D'Avila-Levy, André Luis Souza Dos Santos, Marta Helena Branquinha
A pleiotropic response to the calpain inhibitor MDL28170 was detected in the tomato parasite Phytomonas serpens. Ultrastructural studies revealed that MDL28170 caused mitochondrial swelling, shortening of flagellum and disruption of trans Golgi network. This effect was correlated to the inhibition in processing of cruzipain-like molecules, which presented an increase in expression paralleled by decreased proteolytic activity. Concomitantly, a calcium-dependent cysteine peptidase was detected in the parasite extract, the activity of which was repressed by pre-incubation of parasites with MDL28170...
December 1, 2016: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/27923747/ibulocydine-sensitizes-human-hepatocellular-carcinoma-cells-to-trail-induced-apoptosis-via-calpain-mediated-bax-cleavage
#2
Seok Soon Park, Eunjin Jwa, Seol Hwa Shin, Eun Jin Ju, Intae Park, Jhang Ho Pak, Jung Jin Hwang, Dong-Hyung Cho, B Moon Kim, Sung-Bae Kim, Jung Shin Lee, Si Yeol Song, Seong-Yun Jeong, Eun Kyung Choi
Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) induces apoptosis selectively in cancer cells without affecting the majority of normal human cells. However, hepatocellular carcinoma (HCC) cells often display resistance to TRAIL-induced apoptosis. Ibulocydine (IB) is an isobutyrate ester pro-drug of a novel synthetic Cdk inhibitor that targets Cdk7 and Cdk9. In this study, we show that treatment with subtoxic doses of IB in combination with TRAIL displays potent cytotoxicity in TRAIL-resistant human HCC cells...
December 3, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27913293/differential-role-of-calpain-dependent-protein-cleavage-in-intermediate-and-long-term-operant-memory-in-aplysia
#3
Lisa C Lyons, Jacob S Gardner, Cassidy T Lentsch, Catherine E Gandour, Harini C Krishnan, Eric J Noakes
In addition to protein synthesis, protein degradation or protein cleavage may be necessary for intermediate (ITM) and long-term memory (LTM) to remove molecular constraints, facilitate persistent kinase activity and modulate synaptic plasticity. Calpains, a family of conserved calcium dependent cysteine proteases, modulate synaptic function through protein cleavage. We used the marine mollusk Aplysia californica to investigate the in vivo role of calpains during intermediate and long-term operant memory formation using the learning that food is inedible (LFI) paradigm...
November 29, 2016: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/27910855/l-type-calcium-channels-regulate-filopodia-stability-and-cancer-cell-invasion-downstream-of-integrin-signalling
#4
Guillaume Jacquemet, Habib Baghirov, Maria Georgiadou, Harri Sihto, Emilia Peuhu, Pierre Cettour-Janet, Tao He, Merja Perälä, Pauliina Kronqvist, Heikki Joensuu, Johanna Ivaska
Mounting in vitro, in vivo and clinical evidence suggest an important role for filopodia in driving cancer cell invasion. Using a high-throughput microscopic-based drug screen, we identify FDA-approved calcium channel blockers (CCBs) as potent inhibitors of filopodia formation in cancer cells. Unexpectedly, we discover that L-type calcium channels are functional and frequently expressed in cancer cells suggesting a previously unappreciated role for these channels during tumorigenesis. We further demonstrate that, at filopodia, L-type calcium channels are activated by integrin inside-out signalling, integrin activation and Src...
December 2, 2016: Nature Communications
https://www.readbyqxmd.com/read/27908790/mpp-inhibits-mglur1-5-mediated-long-term-depression-in-mouse-hippocampus-by-calpain-activation
#5
Junyao Li, Hui Chen, Shengbing Wu, Yuefa Cheng, Qinglin Li, Jing Wang, Guoqi Zhu
Neurotoxins are harmful to nervous system and cause either neuronal cell death or impairment of synaptic activity, which contributes to Parkinson's disease or other neuronal disorders. Hippocampal synaptic plasticity was proposed as a cellular model for memory processing. In this study, we reported a novel effect of neurotoxin, 1-methyl-4-phenylpyridinium (MPP(+)), on metabotropic glutamate receptor 1/5 agonist, 3,5-dihydroxyphenylglycine (DHPG)-induced hippocampal synaptic plasticity, and MPP(+) incubation blocked DHPG-induced hippocampal long-term depression (LTD) in Schaffer collateral-CA1 synapses...
November 29, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27906053/attenuated-ca-2-release-in-a-mouse-model-of-limb-girdle-muscular-dystrophy-2a
#6
Marino DiFranco, Irina Kramerova, Julio L Vergara, Melissa Jan Spencer
BACKGROUND: Mutations in CAPN3 cause limb girdle muscular dystrophy type 2A (LGMD2A), a progressive muscle wasting disease. CAPN3 is a non-lysosomal, Ca-dependent, muscle-specific proteinase. Ablation of CAPN3 (calpain-3 knockout (C3KO) mice) leads to reduced ryanodine receptor (RyR1) expression and abnormal Ca2+/calmodulin-dependent protein kinase II (Ca-CaMKII)-mediated signaling. We previously reported that Ca(2+) release measured by fura2-FF imaging in response to single action potential stimulation was reduced in old C3KO mice; however, the use of field stimulation prevented investigation of the mechanisms underlying this impairment...
February 24, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27903970/ion-channels-in-control-of-pancreatic-stellate-cell-migration
#7
Hannah Storck, Benedikt Hild, Sandra Schimmelpfennig, Sarah Sargin, Nikolaj Nielsen, Angela Zaccagnino, Thomas Budde, Ivana Novak, Holger Kalthoff, Albrecht Schwab
Pancreatic stellate cells (PSCs) play a critical role in the progression of pancreatic ductal adenocarcinoma (PDAC). Once activated, PSCs support proliferation and metastasis of carcinoma cells. PSCs even co-metastasise with carcinoma cells. This requires the ability of PSCs to migrate. In recent years, it has been established that almost all "hallmarks of cancer" such as proliferation or migration/invasion also rely on the expression and function of ion channels. So far, there is only very limited information about the function of ion channels in PSCs...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27894956/disulfiram-induces-anoikis-and-suppresses-lung-colonization-in-triple-negative-breast-cancer-via-calpain-activation
#8
Ji Young Kim, Nahyun Lee, Yoon-Jae Kim, Youngkwan Cho, Hyunsook An, Eunhye Oh, Tae-Min Cho, Daeil Sung, Jae Hong Seo
Triple-negative breast cancers (TNBC) often exhibit an aggressive phenotype. Disulfiram (DSF) is an approved drug for the treatment of alcohol dependence, but has also been shown to kill TNBC cells in a copper (Cu)-dependent manner. Exactly how this occurs has not been clearly elucidated. We sought to investigate the mechanisms responsible for DSF/Cu-dependent induction of apoptosis and suppression of lung colonization by TNBC cells. DSF/Cu induced anoikis and significantly suppressed cell migration and invasion with negative effects on focal adhesions, coinciding with vimentin breakdown and calpain activation in TNBC cells...
November 25, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27881674/a-gastrointestinal-calpain-complex-g-calpain-is-a-heterodimer-of-capn8-and-capn9-which-play-catalytic-and-regulatory-roles-respectively
#9
Shoji Hata, Fujiko Kitamura, Midori Yamaguchi, Hiroshi Shitara, Makoto Murakami, Hiroyuki Sorimachi
Calpains (CAPN) are a family of Ca(2+)-dependent cysteine proteases that regulate various cellular functions by cleaving diverse substrates. Of the 15 mammalian calpains, CAPN8 and CAPN9 are two that are expressed predominantly in the gastrointestinal tract, where they interact to form a protease complex, termed G-calpain. However, because native G-calpain exhibits a highly restricted expression pattern, it has never been purified, and the interactions between CAPN8 and CAPN9 have not been characterized. Here, we clarified the molecular nature of G-calpain by using recombinant proteins and transgenic mice expressing Flag-tagged CAPN8 (CAPN8-Flag)...
November 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27880847/activation-of-both-the-calpain-and-ubiquitin-proteasome-systems-contributes-to-septic-cardiomyopathy-through-dystrophin-loss-disruption-and-mtor-inhibition
#10
Ana Caroline Silva Freitas, Maria Jose Figueiredo, Erica Carolina Campos, Danilo Figueiredo Soave, Simone Gusmao Ramos, Herbert B Tanowitz, Mara Rúbia N Celes
Cardiac dysfunction caused by the impairment of myocardial contractility has been recognized as an important factor contributing to the high mortality in sepsis. Calpain activation in the heart takes place in response to increased intracellular calcium influx resulting in proteolysis of structural and contractile proteins with subsequent myocardial dysfunction. The purpose of the present study was to test the hypothesis that increased levels of calpain in the septic heart leads to disruption of structural and contractile proteins and that administration of calpain inhibitor-1 (N-acetyl-leucinyl-leucinyl-norleucinal (ALLN)) after sepsis induced by cecal ligation and puncture prevents cardiac protein degradation...
2016: PloS One
https://www.readbyqxmd.com/read/27878263/capn4-promotes-epithelial-mesenchymal-transition-in-human-melanoma-cells-through-activation-of-the-wnt-%C3%AE-catenin-pathway
#11
Enwen Wang, Donglin Wang, Bing Li, Huiwen Ma, Chunmei Wang, Lili Guan, Haiwei Zhang, Lin Yi, Shaolin Li
Melanoma, as one of the most highly metastatic types of cancer, is resistant to current treatment methods, including popular targeted molecular therapy. Consequently, it is essential to develop a deeper understanding of the mechanisms involved in melanoma progression so that alternative treatments may be identified. To date, accumulating evidence supports the use of calpains, including calpain small subunit 1 (also known as Capn4 or CAPNS1), which affect cancer progression through many pathways, such as epithelial‑mesenchymal transition (EMT), the Wnt/β-catenin (β-catenin) and the nuclear factor κB (NF-κB) signaling pathways...
November 15, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27875293/attenuation-of-blood-brain-barrier-breakdown-and-hyperpermeability-by-calpain-inhibition
#12
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/27872190/ptp1b-in-calpain-dependent-feedback-regulation-of-vegfr2-in-endothelial-cells-implication-in-vegf-dependent-angiogenesis-and-diabetic-wound-healing
#13
Yixuan Zhang, Qiang Li, Ji Youn Youn, Hua Cai
The VEGF/VEGFR2/Akt/eNOS/NO pathway is essential to VEGF-induced angiogenesis. We have previously discovered a novel role of calpain in mediating VEGF-induced PI3K/AMPK/Akt/eNOS activation through Ezrin. Here, we sought to identify possible feedbak regulation of VEGFR2 by calpain via its substrate protein phosphotyrosine phosphatase 1B (PTP1B), and the relevance of this pathway to VEGF-induced angiogenesis, especially in diabetic wound healing. Over-expression of PTP1B inhibited VEGF-induced VEGFR2 and Akt phosphorylation in bovine aortic endothelial cells, while PTP1B siRNA increased both, implicating the negative regulation of VEGFR2 by PTP1B...
November 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27869056/why-calpain-inhibitors-are-interesting-leading-compounds-to-search-for-new-therapeutic-options-to-treat-leishmaniasis
#14
Vitor Ennes-Vidal, Rubem Figueiredo Sadock Menna-Barreto, Marta Helena Branquinha, André Luis Souza Dos Santos, Claudia Masini D'Avila-Levy
Leishmaniasis is a neglected disease, which needs improvements in drug development, mainly due to the toxicity, parasite resistance and low compliance of patients to treatment. Therefore, the development of new chemotherapeutic compounds is an urgent need. This opinion article will briefly highlight the feasible use of calpain inhibitors as leading compounds to search for new therapeutic options to treat leishmaniasis. The milestone of this approach is to take advantage on the myriad of inhibitors developed against calpains, some of which are in advanced clinical trials...
November 21, 2016: Parasitology
https://www.readbyqxmd.com/read/27865555/calpain-inhibitors-the-aspirin-of-the-21st-century
#15
EDITORIAL
Juan A Crestanello
No abstract text is available yet for this article.
October 24, 2016: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/27862930/piperine-inhibits-abca1-degradation-and-promotes-cholesterol-efflux-from-thp-1-derived-macrophages
#16
Limei Wang, Veronika Palme, Susanne Rotter, Nicole Schilcher, Malsor Cukaj, Dongdong Wang, Angela Ladurner, Elke H Heiss, Herbert Stangl, Verena M Dirsch, Atanas G Atanasov
SCOPE: Increased macrophage cholesterol efflux is considered to have anti-atherosclerotic effect counteracting cardiovascular disease. The principle pungent ingredient of the fruits of Piper nigrum, piperine, is identified in this study as a cholesterol efflux (ChE) inducer in THP-1-derived macrophages, and mechanisms underlying this effect are explored. METHODS AND RESULTS: Without affecting cell viability, piperine concentration-dependently enhances ChE in THP-1-derived macrophages from 25 to 100 μM...
November 15, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27859240/the-neuroprotective-effect-of-latanoprost-acts-via-klotho-mediated-suppression-of-calpain-activation-after-optic-nerve-transection
#17
Kotaro Yamamoto, Kota Sato, Masayoshi Yukita, Masayuki Yasuda, Kazuko Omodaka, Morin Ryu, Kosuke Fujita, Koji M Nishiguchi, Shigeki Machida, Toru Nakazawa
Latanoprost was first developed for use in glaucoma therapy as an ocular hypotensive agent targeting the prostaglandin F2α (FP) receptor. Subsequently, latanoprost showed a neuroprotective effect, an additional pharmacological action. However, although it is well known that latanoprost exerts an ocular hypotensive effect via the FP receptor, it is not known whether this is also true of its neuroprotective effect. Klotho was firstly identified as the gene linked to the suppression of ageing phenotype: the defect of klotho gene in mice results ageing phenotype such as hypokinesis, arteriosclerosis and short lifespan...
November 15, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27857681/early-cytoskeletal-protein-modifications-precede-overt-structural-degeneration-in-the-dba-2j-mouse-model-of-glaucoma
#18
Gina N Wilson, Matthew A Smith, Denise M Inman, Christine M Dengler-Crish, Samuel D Crish
Axonal transport deficits precede structural loss in glaucoma and other neurodegenerations. Impairments in structural support, including modified cytoskeletal proteins, and microtubule-destabilizing elements, could be initiating factors in glaucoma pathogenesis. We investigated the time course of changes in protein levels and post-translational modifications in the DBA/2J mouse model of glaucoma. Using anterograde tract tracing of the retinal projection, we assessed major cytoskeletal and transported elements as a function of transport integrity in different stages of pathological progression...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27852058/ischemic-preconditioning-attenuates-ischemia-reperfusion-injury-in-rat-steatotic-liver-role-of-heme-oxygenase-1-mediated-autophagy
#19
Anding Liu, Enshuang Guo, Jiankun Yang, Renlong Li, Yan Yang, Shenpei Liu, Jifa Hu, Xiaojing Jiang, Olaf Dirsch, Uta Dahmen, Jian Sun, Mingwen Ouyang
Steatotic livers are more susceptible to ischemia/reperfusion (I/R) injury, which is ameliorated by ischemic preconditioning (IPC). Autophagy possesses protective action on liver I/R injury and declines in steatotic livers. The aim of this study was to test the hypothesis that the increased susceptibility of steatotic livers to I/R injury was associated with defective hepatic autophagy, which could be restored by IPC via heme oxygenase-1 (HO-1) signaling. Obesity and hepatic steatosis was induced using a high fat diet...
November 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27851790/functional-effect-of-the-mutations-similar-to-the-cleavage-during-platelet-activation-at-integrin-%C3%AE-3-cytoplasmic-tail-when-expressed-in-mouse-platelets
#20
Xiaofeng Shi, Jichun Yang, Xiongying Cui, Jiansong Huang, Zhangbiao Long, Yulan Zhou, Ping Liu, Lanlan Tao, Zheng Ruan, Bing Xiao, Wei Zhang, Dongya Li, Kesheng Dai, Jianhua Mao, Xiaodong Xi
Previous studies in Chinese hamster ovary cells showed that truncational mutations of β3 at sites of F754 and Y759 mimicking calpain cleavage regulate integrin signaling. The roles of the sequence from F754 to C-terminus and the conservative N756ITY759 motif in platelet function have yet to be elaborated. Mice expressing β3 with F754 and Y759 truncations, or NITY deletion (β3-ΔTNITYRGT, β3-ΔRGT, or β3-ΔNITY) were established through transplanting the homozygous β3-deficient mouse bone marrow cells infected by the GFP tagged MSCV MigR1 retroviral vector encoding different β3 mutants into lethally radiated wild-type mice...
2016: PloS One
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