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Naira F Z Schneider, Claudia Cerella, Jin-Young Lee, Aloran Mazumder, Kyung Rok Kim, Annelise de Carvalho, Jennifer Munkert, Rodrigo M Pádua, Wolfgang Kreis, Kyu-Won Kim, Christo Christov, Mario Dicato, Hyun-Jung Kim, Byung Woo Han, Fernão C Braga, Cláudia M O Simões, Marc Diederich
Cardiac glycosides (CGs) are natural compounds used traditionally to treat congestive heart diseases. Recent investigations repositioned CGs as potential anticancer agents. To discover novel cytotoxic CG scaffolds, we selected the cardenolide glucoevatromonoside (GEV) out of 46 CGs for its low nanomolar anti-lung cancer activity. GEV presented reduced toxicity toward non-cancerous cell types (lung MRC-5 and PBMC) and high-affinity binding to the Na+ /K+ -ATPase α subunit, assessed by computational docking...
2018: Frontiers in Pharmacology
Andreas Kling, Katja Jantos, Helmut Mack, Wilfried Hornberger, Gisela Backfisch, Yanbin Lao, Marjoleen Nijsen, Beatrice Rendenbach-Mueller, Achim Moeller
Dysregulation of calpains 1 and 2 has been implicated in a variety of pathological disorders including ischemia/reperfusion injuries, kidney diseases, cataract formation, and neurodegenerative diseases such as Alzheimer's disease (AD). 2-(3-Phenyl-1 H )-pyrazol-1-yl)nicotinamides represent a series of novel and potent calpain inhibitors with high selectivity and in vivo efficacy. However, carbonyl reduction leading to the formation of the inactive hydroxyamide was identified as major metabolic liability in monkey and human, a pathway not reflected by routine absorption, distribution, metabolism, and excretion (ADME) assays...
March 8, 2018: ACS Medicinal Chemistry Letters
Qiang Wang, Akram A Da'dara, Patrick J Skelly
BACKGROUND: Schistosomes are blood dwelling parasitic worms that cause the debilitating disease schistosomiasis. Here we examined the influence of the parasites on their external environment by monitoring the impact of adult Schistosoma mansoni worms on the murine plasma proteome in vitro and, in particular, on how the worms affect the blood coagulation protein high molecular weight kininogen (HK). METHODS: Following the incubation of adult schistosomes in murine plasma, two-dimensional differential in-gel electrophoresis (2D-DIGE) was conducted to look for changes in the plasma proteome compared with control plasma...
March 14, 2018: Parasites & Vectors
Meiling Yan, Kankai Chen, Li He, Shuai Li, Dong Huang, Jingbo Li
BACKGROUND/AIMS: Hyperuricemia is associated with an increased risk for multiple cardiovascular diseases, but the underlying mechanisms remain largely elusive. Calpain-1 is a protease that is implicated in several pathological conditions that affect the heart. The aim of this current study was to test the effects of uric acid (UA) on cardiomyocyte survival and cardiac function and to investigate the role of calpain-1 in the UA-induced effects in the heart and their underlying mechanisms...
March 7, 2018: Cellular Physiology and Biochemistry
Xiaohua Wang, Cheng Chen, Guoren Zhou, Jinjun Ye, Rong Yin, Dongjie Feng, Shuai Zhang, Xiaojun Wang, Xin Zhao, Zhi Zhang
BACKGROUND/AIMS: Our previous study suggested the anti-tumor activity of sepia ink oligopeptide (SIO). Here we sought to investigate the underlying molecular mechanism. METHODS: Cell proliferation was evaluated by cell counting kit-8 (CCK-8) assay. Cell apoptosis was determined by Annexin V/Propidium Iodide (PI) staining. The mitochondria pathway was characterized by quantification of Bcl-2, Bax, Caspase-9 and Cyto-C. The death receptor pathway was analyzed by determinement of Fas, Caspase-8 and NIK...
March 7, 2018: Cellular Physiology and Biochemistry
Traci Cramer, Moriah L Penick, Jolena N Waddell, Chris A Bidwell, Yuan H Brad Kim
The objective of this study was to determine associations of small heat shock proteins (sHSPs) in tenderness development of loins from callipyge and normal genotype lambs. Loins (M. longissimus lumborum) from sixteen lambs across four genotypes were collected throughout 9 days of postmortem aging. The loins from callipyge lambs had more intact desmin and troponin T throughout aging periods, as well as less μ-calpain autolysis and more calpastatin compared to loins from other genotypes (P < 0.05). Delayed onset of apoptosis was found in the callipyge loins indicated by less cytochrome c and more inactive procaspase-3 compared to normal lamb loins (P < 0...
March 6, 2018: Meat Science
Debika Datta, Preeti Khatri, Ambika Singh, Dhira Rani Saha, Gaurav Verma, Rajagopal Raman, Shibnath Mazumder
Mycobacterium fortuitum is a natural fish pathogen. It induces apoptosis in headkidney macrophages (HKM) of catfish, Clarias sp though the mechanism remains largely unknown. We observed M. fortuitum triggers calcium (Ca2+ ) insult in the sub-cellular compartments which elicits pro-apototic ER-stress factor CHOP. Alleviating ER-stress inhibited CHOP and attenuated HKM apoptosis implicating ER-stress in the pathogenesis of M. fortuitum . ER-stress promoted calpain activation and silencing the protease inhibited caspase-12 activation...
December 2018: Cell Death Discovery
Irina Kramerova, Jorge A Torres, Ascia Eskin, Stanley F Nelson, Melissa J Spencer
Mutations in CAPN3 cause autosomal recessive limb girdle muscular dystrophy 2A. Calpain 3 (CAPN3) is a calcium dependent protease residing in the myofibrillar, cytosolic and triad fractions of skeletal muscle. At the triad, it colocalizes with calcium calmodulin kinase IIβ (CaMKIIβ). CAPN3 knock out mice (C3KO) show reduced triad integrity and blunted CaMKIIβ signaling, which correlates with impaired transcriptional activation of myofibrillar and oxidative metabolism genes in response to running exercise...
March 8, 2018: Human Molecular Genetics
Benyu Su, Qiangdong Guan, Miaomiao Wang, Ning Liu, Xiaomin Wei, Shue Wang, Xiwei Yang, Wenchong Jiang, Mengmeng Xu, Sufang Yu
The aim of this study is to explore the potent neuroprotective effect of calpeptin (CP) on neuron damage induced by acrylamide (ACR) and its mechanism. Behavioural indicators such as hind limb splay, rota-rod performance, and gait analysis were assessed weekly to evaluate neurobehavioural changes after ACR and/or CP administration. The histopathological alterations and the changes of μ-calpain, m-calpain, microtubule-associated protein 2 (MAP2), and α-tubulin and β-tubulin protein levels in spinal cord were determined...
March 7, 2018: Toxicology
Akiomi Yoshihisa, Yusuke Kimishima, Takatoyo Kiko, Yu Sato, Shunsuke Watanabe, Yuki Kanno, Satoshi Abe, Makiko Miyata, Takamasa Sato, Satoshi Suzuki, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Takafumi Ishida, Yasuchika Takeishi
Titin is associated with myocardial stiffness and hypertrophy, and mutations in its gene have been identified in cardiac myopathies such as dilated cardiomyopathy (DC). It has recently been reported that in damaged muscle, the N-terminal fragment of titin (Titin-N) is cleaved by calpain-3, and urinary Titin-N (U-TN) could be a marker of sarcomere damage. We aimed to investigate the impact of U-TN on prognosis of DC. We measured urinary levels of Titin-N/creatinine ratio (U-TN/Cr; pmol/mg/dl) in 102 patients with DC, and followed up all the patients (mean 1,167 days)...
February 12, 2018: American Journal of Cardiology
Jie-Qiong Ma, Chan-Min Liu, Wei Yang
Rutin, a natural flavonoid, possess beneficial health effects. However, its renoprotective effect against carbon tetrachloride (CCl4 ) induced injury and the underlying mechanism is not clarified. The current study aims is to identify the therapeutic effects of rutin on oxidative stress, inflammation and apoptosis in mouse kidney exposed to CCl4 . ICR mice received CCl4 with or without rutin co-administration for one week. Compared with the control group, mice receiving CCl4 alone showed kidney injury as evidenced by elevation in serum biochemical markers, inflammation, caspase-3 activity and apoptosis in kidney, while rutin administration significantly attenuated these pathophysiological changes...
March 6, 2018: Chemico-biological Interactions
Joel D Leal-Gutiérrez, Mauricio A Elzo, Dwain D Johnson, Tracy L Scheffler, Jason M Scheffler, Raluca G Mateescu
Autogenous proteolytic enzymes of the calpain family are implicated in myofibrillar protein degradation. As a result, the μ-calpain gene and its specific inhibitor, calpastatin, have been repeatedly investigated for their association with meat quality traits in cattle; however, no functional mutation has been identified for these two genes. The objectives of this study were: (1) to assess breed composition effect on tenderness; (2) to perform a linkage disequilibrium (LD) analysis in μ-calpain and calpastatin genes as well as an association analyses with tenderness; and (3) to analyze putative functional SNPs inside the significant LD block for an effect on tenderness...
2018: Frontiers in Genetics
Arkadiy Reunov, Anatoliy Reunov, Evgenia Pimenova, Yulia Reunova, Ekaterina Menchinskaiya, Larisa Lapshina, Dmitry Aminin
An expression of calpain and caspase-1 as well as the concomitant ultrastructural alterations were investigated during necrosis of the mouse Ehrlich ascites carcinoma. The calpain expression was registered at 0 h and 1 h although caspase-1 did not induce any signals during these time periods. The rise of the cytoplasmic lytic zones contacted by calpain antibodies was identified as a morphologic event corresponding to the expression of calpain. Lytic zone's distribution followed by the appearance of the calpain/caspase-1 clusters assigned for lysis of the Golgi vesicles and ER...
March 5, 2018: Gene
Awen Menou, JanWillem Duitman, Bruno Crestani
Idiopathic Pulmonary Fibrosis (IPF) is a devastating chronic, progressive and irreversible disease that remains refractory to current therapies. Matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of MMPs (TIMPs), have been implicated in the development of pulmonary fibrosis since decades. Coagulation signalling deregulation, which influences several key inflammatory and fibro-proliferative responses, is also essential in IPF pathogenesis, and a growing body of evidence indicates that Protease-Activated Receptors (PARs) inhibition in IPF may be promising for future evaluation...
March 5, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
Marcelino Telechea-Fernández, Lucia Rodríguez-Fernández, Concha García, Rosa Zaragozá, Juan Viña, Andrés Cervantes, Elena R García-Trevijano
Calpain-2 belongs to a family of pleiotropic Cys-proteases with modulatory rather than degradative functions. Calpain (CAPN) overexpression has been controversially correlated with poor prognosis in several cancer types, including colorectal carcinoma (CRC). However, the mechanisms of substrate-recognition, calpain-2 regulation/deregulation and specific functions in CRC remain elusive. Herein, calpain subcellular distribution was studied as a key event for substrate-recognition and consequently, for calpain-mediated function...
February 6, 2018: Oncotarget
Styliani Goulopoulou
No abstract text is available yet for this article.
March 5, 2018: Hypertension
Zienab Etwebi, Gavin Landesberg, Kyle Preston, Satoru Eguchi, Rosario Scalia
MPO (myeloperoxidase) is a peroxidase enzyme secreted by activated leukocytes that plays a pathogenic role in cardiovascular disease, mainly by initiating endothelial dysfunction. The molecular mechanisms of the endothelial damaging action of MPO remain though largely elusive. Calpain is a calcium-dependent protease expressed in the vascular wall. Activation of calpains has been implicated in inflammatory disorders of the vasculature. Using endothelial cells and genetically modified mice, this study identifies the µ-calpain isoform as novel downstream signaling target of MPO in endothelial dysfunction...
April 2018: Hypertension
Anna Gabriela Castro-Martínez, José Sánchez-Corona, Adriana Patricia Vázquez-Vargas, Alejandra Guadalupe García-Zapién, Andres López-Quintero, Héctor Javier Villalpando-Velazco, Silvia Esperanza Flores-Martínez
Gestational diabetes mellitus (GDM) is a metabolically complex disease with major genetic determinants. GDM has been associated with insulin resistance and dysfunction of pancreatic beta cells, so the GDM candidate genes are those that encode proteins modulating the function and secretion of insulin, such as that for calpain 10 (CAPN10). This study aimed to assess whether single nucleotide polymorphism (SNP)-43, SNP-44, SNP-63, and the indel-19 variant, and specific haplotypes of the CAPN10 gene were associated with gestational diabetes mellitus...
February 28, 2018: Cellular and Molecular Biology
Jianjun Zhu, Mingpeng Jin, Jiaojiao Wang, Hui Zhang, Yousheng Wu, Deyang Li, Xiaoying Ji, Hushan Yang, Chun Yin, Tingting Ren, Jinliang Xing
BACKGROUND: Tumor necrosis factor-α has been proven an effective anticancer agent in preclinical studies. However, the translation of TNFα from research to clinic has been blocked by significant systemic toxicity and limited efficacy at maximal tolerated dose, which need urgently to be solved. METHODS: The level of cytosolic Ca2+ was assessed by Fura-2 in HCC cells. After changing cytosolic Ca2+ level by using agonists or inhibitors, cell apoptosis was detected by flow cytometry...
March 5, 2018: Journal of Experimental & Clinical Cancer Research: CR
Ngonidzashe B Madungwe, Yansheng Feng, Mihaela Lie, Nathalie Tombo, Li Liu, Ferdinand Kaya, Jean C Bopassa
Mitofilin is an inner membrane protein that has been defined as a mitochondria-shaping protein in controlling and maintaining mitochondrial cristae structure and remodeling. We determined the role of mitofilin in cell survival by investigating the mechanism underlying mitofilin knockdown-induced cell death by apoptosis. Cultured H9c2 myoblasts and HEK 293 cells were treated with mitofilin siRNA or scrambled siRNA for 24 hours. Cell death (apoptosis), caspase 3 activity, and cell cycle phases were assessed by flow cytometry, while cytochrome C release and intracellular ATP production were measured by ELISA...
February 28, 2018: American Journal of Physiology. Cell Physiology
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