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Ron Bochner, Liat Samuelov, Ofer Sarig, Qiaoli Li, Christopher A Adase, Ofer Isakov, Natalia Malchin, Dan Vodo, Ronna Shayevitch, Alon Peled, Benjamin D Yu, Gilad Fainberg, Emily Warshauer, Noam Adir, Noam Erez, Andrea Gat, Yehonatan Gottlieb, Tova Rogers, Mor Pavlovsky, Ilan Goldberg, Noam Shomron, Aileen Sandilands, Linda E Campbell, Stephanie MacCallum, W H Irwin McLean, Gil Ast, Richard L Gallo, Jouni Uitto, Eli Sprecher
Congenital erythroderma is a rare and often life-threatening condition, which has been shown to result from mutations in several genes encoding important components of the epidermal differentiation program. Using whole exome sequencing, we identified in a child with congenital exfoliative erythroderma, hypotrichosis, severe nail dystrophy and failure to thrive, two heterozygous mutations in ABCA12 (c.2956C>T, p.R986W; c.5778+2T>C, p. G1900Mfs*16), a gene known to be associated with 2 forms of ichthyosis, autosomal recessive congenital ichthyosis and harlequin ichthyosis...
October 18, 2016: Journal of Investigative Dermatology
Elizabeth E Hjort, Weiqi Huang, Liping Hu, Elizabeth A Eklund
Icsbp/Irf8 is an interferon regulatory transcription factor that functions as a suppressor of myeloid leukemias. Consistent with this activity, Icsbp represses a set of genes encoding proteins that promote cell proliferation/survival. One such gene encodes Gas2, a calpain inhibitor. We previously found that increased Gas2-expression in Bcr-abl+ cells stabilized βcatenin; a Calpain substrate. This was of interest, because βcatenin contributes to disease progression in chronic myeloid leukemia (CML). Calpain has additional substrates implicated in leukemogenesis, including Stat5...
October 19, 2016: Oncotarget
Lingfeng Meng, Albert Zhang, Yishi Jin, Dong Yan
Axon specification is a critical step in neuronal development, and the function of glial cells in this process is not fully understood. Here we show that C. elegans GLR glial cells regulate axon specification of their nearby GABAergic RME neurons through GLR-RME gap junctions. Disruption of GLR-RME gap junctions causes misaccumulation of axonal markers in non-axonal neurites of RME neurons and converts microtubules in those neurites to form an axon-like assembly. We further uncover that GLR-RME gap junctions regulate RME axon specification through activation of the CDK-5 pathway in a calcium-dependent manner, involving a calpain clp-4...
October 21, 2016: ELife
Jinxin Xie, Huancheng Guo, Wenjie Gong, Daliang Jiang, Li Zhang, Junjie Jia, Changchun Tu
NS5A is a multifunctional non-structural protein of classical swine fever virus (CSFV) that plays an important role in viral replication, but how it exerts its functions is unknown. Here, we report the cleavage of NS5A of the vaccine C-strain, resulting in two truncated forms (b and c). Further experiments using calpain- and caspase-family-specific inhibitors, followed by a caspase-6-specific shRNAs and inhibitor, showed that the cleavage of C-strain NS5A to produce truncated form c is mediated by caspase-6, mapping to (272)DTTD(275), while the cleavage producing truncated form b is probably mediated by another unknown protease...
October 20, 2016: Archives of Virology
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
Zenei Taira, Yukari Ueda, Hiroshi Monmasu, Daisuke Yamase, Sayaka Miyake, Maya Shiraishi
Two specific signals for regulating liver regeneration were found after 70% partial hepatectomy (PH) in rats. The first finding was a sustained increasing signal of intracellular Ca(2+) ([Ca(2+)]i) in hepatocytes, consisting of two successive peaks with the first narrow peak at 1 hour and the second broad peak increasing by day 3 and then returning to normal by day 4. The second finding was an abnormal peak in the restoring ratio (Rr) curve of liver regeneration after 70% PH at day 4, where the Rr exceeded 100% temporarily, returned to a lower level, and then proceeded to a termination phase of liver regeneration...
2016: Journal of Experimental Pharmacology
Dhika Amanda, Monika Susanne Doblin, Roberta Galletti, Antony Bacic, Gwyneth C Ingram, Kim L Johnson
The plant epidermis is crucial to survival, regulating interactions with the environment and controlling plant growth. The phytocalpain DEFECTIVE KERNEL1 (DEK1) is a master regulator of epidermal differentiation and maintenance, acting upstream of epidermal-specific transcription factors, and is required for correct cell adhesion. It is currently unclear how changes in DEK1 lead to cellular defects in the epidermis and the pathways through which DEK1 acts. We have combined growth kinematic studies, cell wall analysis and transcriptional analysis of genes downstream of DEK1 to determine the cause of phenotypic changes observed in DEK1-modulated lines...
October 17, 2016: Plant Physiology
Shuang Chen, Jie Yan, Hai-Xiao Deng, Ling-Ling Long, Yong-Jun Hu, Mi Wang, Lei Shang, Dan Chen, Ju-Fang Huang, Kun Xiong
The purpose of this study was to investigate the effect of inhibition of calpain on retinal ganglion cell-5 (RGC-5) necroptosis following oxygen glucose deprivation (OGD). RGC-5 cells were cultured in Dulbecco's-modified essential medium and necroptosis was induced by 8-h OGD. PI staining and flow cytometry were performed to detect RGC-5 necrosis. The calpain expression was detected by Western blotting and immunofluorescence staining. The calpain activity was tested by activity detection kit. Flow cytometry was used to detect the effect of calpain on RGC-5 necroptosis following OGD with or without N-acetyl-leucyl-leucyl-norleucinal (ALLN) pre-treatment...
October 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
Dan-Dan Wu, Xing-Heng Wu, Li-Na Zhang
OBJECTIVE: To study the effect of leptin on the expression of calcium-activated neutral protease 1 (calpain-1) and B cell lymphoma-2 (Bcl-2) and apoptosis in the myocardial tissue of neonatal rats after asphyxia. METHODS: A total of 48 neonatal rats were randomly and equally divided into normal control group, asphyxia group, leptin treatment groups, and calpain-1 inhibitor (CAI-1) group. The neonatal rat model of asphyxia under normal atmospheric condition was established in all groups except the control group...
October 2016: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
John E Cebak, Indrapal N Singh, Rachel L Hill, Juan Wang, Edward D Hall
Lipid peroxidation is a key contributor to the pathophysiology of traumatic brain injury (TBI). Traditional antioxidant therapies are intended to scavenge the free radicals responsible for either the initiation or the propagation of lipid peroxidation (LP). A more recently explored approach involves scavenging the terminal LP breakdown products that are highly reactive and neurotoxic carbonyl compounds 4-hydroxynonenal (4-HNE) and acrolein to prevent their covalent modification and rendering of cellular proteins non-functional leading to loss of ionic homeostasis, mitochondrial failure, and subsequent neuronal death...
October 18, 2016: Journal of Neurotrauma
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
Chiung-Yueh Hsu, Géraldine Gasc, Anne-Aurélie Raymond, Odile Burlet-Schiltz, Hidenari Takahara, Guy Serre, Marie-Claire Méchin, Michel Simon
Hornerin (HRNR) shares numerous features with filaggrin, a key contributor to the epidermal barrier functions. The two proteins display a related structural organization, are expressed by the granular keratinocytes as a large precursor processed by proteolysis, and are cross-linked to the cornified cell envelopes. Two main steps in the metabolism of filaggrin are its deimination and calpain-1 cleavage. Here, using ion-exchange chromatography and two-dimensional gel electrophoresis of human epidermis extracts, we determined that HRNR is deiminated in vivo...
October 11, 2016: Journal of Investigative Dermatology
Xueyan Yang, Meihui Yin, Lan Yu, Meili Lu, Hongxin Wang, Futian Tang, Yingjie Zhang
We previously reported that simvastatin, an inhibitor of HMG-CoA reductase, inhibits atherosclerosis in rats. The present study was designed to investigate the effect of simvastatin on mouse peritoneal macrophage foam cell formation, the early feature of atherosclerosis, and explore its mechanisms. The results showed that simvastatin decreased cholesterol content and DiI-oxLDL (1,1'-didodecyl 3,3,3',3'-indocarbocyanine perchlorate - oxidized low-density lipoprotein) uptake, reduced the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the medium, down-regulated the mRNA and protein expression of CD36 (a fatty acid receptor), and reduced the mRNA expressions of peroxisome proliferator-activated receptor gamma (PPARγ), TNF-α, and IL-6 in macrophages treated with oxLDL...
August 16, 2016: Canadian Journal of Physiology and Pharmacology
Lygia M Malvestio, Mara Rúbia N Celes, Linda A Jelicks, Herbert B Tanowitz, Cibele M Prado
Dystrophin, an important protein of the dystrophin-glycoprotein complex, has been implicated in the pathogenesis of experimental Chagas disease. It is important for the maintenance of cell shape and contraction force transmission. Dystrophin loss has been related to end-stage cardiac myopathies and proposed as a common route for myocardial dysfunction and progression to advanced heart failure. Evidence suggests that calpains, calcium-dependent proteases, digest dystrophin when the calcium concentration is compatible with their activation...
October 11, 2016: Parasitology Research
Krit Jaikumkao, Anchalee Pongchaidecha, La-Ongdao Thongnak, Keerati Wanchai, Phatchawan Arjinajarn, Varanuj Chatsudthipong, Nipon Chattipakorn, Anusorn Lungkaphin
Gentamicin is a commonly used aminoglycoside antibiotic. However, its therapeutic use is limited by its nephrotoxicity. The mechanisms of gentamicin-induced nephrotoxicity are principally from renal inflammation and oxidative stress. Since atorvastatin, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, exerts lipid-lowering effects, antioxidant, anti-inflammatory as well as anti-apoptotic effects, this study aimed to investigate the protective effects of atorvastatin against gentamicin-induced nephrotoxicity...
2016: PloS One
Zheng Li, Xin Li, Xing Gao, Qingwu W Shen, Manting Du, Dequan Zhang
Myofibrillar proteins degradation contributes to meat tenderisation during post-mortem ageing. Protein phosphorylation has been revealed to be associated with meat tenderness in recent years. This study was undertaken to determine the impact of myofibrillar proteins phosphorylation on the degradation susceptibility by μ-calpain. Myofibrillar proteins were first incubated with protein kinase A (PKA) or alkaline phosphatase (AP) to increase or decrease the phosphorylation level, following μ-calpain hydrolysis...
March 1, 2017: Food Chemistry
Youjun Li, Xiaoyong Luo, Yang Sun, Zhenyi Cui, Yizhou Liu, Rushi Liu, Xiangrong Guo
Focal adhesions are large multi-protein complexes that serve as the linkage between extracellular matrix (ECM) and actin cytoskeleton and control the network of signaling cascades underlying cell migration. Talin plays a key role in focal adhesion turnover, and calpain-mediated proteolysis of talin is central to focal adhesion disassembly, but its regulation is not well elucidated. Here we demonstrate that talin phosphorylation at three high stoichiometry sites on its head domain, T144 and T150, or S446, have contrasting effects on calpain-mediated cleavage of talin and cell migration by using site-directed mutagenesis to inhibit phosphorylation...
2016: Journal of Cancer
Sarinthorn Thummayot, Chainarong Tocharus, Apichart Suksamrarn, Jiraporn Tocharus
This study evaluated the mechanisms underlying the protective effect of cyanidin against Aβ25-35-induced neuronal cell death in SK-N-SH cells. Aβ25-35-induced neurotoxicity is characterized by a decrease in cell viability, inducing the expression of endoplasmic reticulum (ER) stress proteins; an increase in intracellular reactive oxygen species (ROS) production; and an increase in intracellular calcium release. Aβ25-35 also induces neuronal toxicity through the disturbance of ER calcium levels. Pretreatment with cyanidin significantly attenuated the Aβ25-35-induced loss of cell viability, reducing the expression of endoplasmic reticulum (ER) stress response proteins with regard to the down-regulation of the expression levels of 78 kDa glucose regulated protein (Grp78), phosphorylated forms of pancreatic ER elF2α kinase (PERK), eukaryotic initiation factor 2 α (eIF2α), and inositol-requiring enzyme 1 (IRE1), and the expression levels of X-box binding protein 1 (XBP-1), activating transcription factor 6 (ATF6), and CCAAT/enhancer binding protein homologous transcription factor (C/EBP) homologous protein (CHOP); decreased intracellular ROS production; decreased intracellular calcium release; and reduced down-regulation of the protein expression levels of calpain and cleaved caspase-12...
September 30, 2016: Neurochemistry International
Tomoyuki Yuasa, Kikuko Amo-Shiinoki, Shuhei Ishikura, Mitsuyoshi Takahara, Takaaki Matsuoka, Hideaki Kaneto, Akio Kuroda, Munehide Matsuhisa, Seiichi Hashida
AIMS/HYPOTHESIS: Soluble insulin receptor (sIR), the ectodomain of the insulin receptor (IR), has been detected in human plasma and its concentration paralleled that of blood glucose. We have previously developed an in vitro model using HepG2 liver-derived cells, which mimics changes in sIR levels in plasma from diabetic patients and shows that calcium-dependent proteases cleave IR extracellularly (a process known as shedding). The present study aimed to reveal the mechanisms of IR cleavage...
September 30, 2016: Diabetologia
Yijie Chen, Yang Yu, Shuya Sun, Zhaotong Wang, Peiqing Liu, Shenglan Liu, Jianmin Jiang
Tumor metastasis is the main reason of death for hepatocellular carcinoma (HCC) patients. Cell migration and invasion are two prerequisites for tumor metastasis, in which TRPM7 and MMPs play an important role. In our study, we found that bradykinin (BK) could upregulate the expression of TRPM7 and dynamically regulate the phosphorylation of non-muscle myosin IIA heavy chain (NMHC-IIA) Ser-1943 in HepG2 cells. The influx of Ca(2+) via TRPM7 was necessary for elevating the activity of m-calpain and μ-calpain...
September 30, 2016: Experimental Cell Research
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