Redox-active metal-induced release of high mobility group box 1(HMGB1) and inflammatory cytokines in fibroblast-like synovial cells is Toll-like receptor 4 (TLR4) dependent
Publication date: Available online 25 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Asmaa A. Alsousi, Orisa J. IgweAbstractRheumatoid arthritis (RA) is a chronic autoimmune systemic inflammatory disease that is characterized by synovial inflammation and bone erosion. We have investigated the mechanism(s) by which essential trace metals may initiate and propagate inflammatory phenotypes in synovial fibroblasts. We used HIG-82, rabbit fibroblast-like synovial cells (FLS), as a model system for potentially initiating RA through oxidative stress. We used potassium peroxychromate ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 25, 2018 Category: Molecular Biology Source Type: research

Exosomal Mst1 transfer from cardiac microvascular endothelial cells to cardiomyocytes deteriorates diabetic cardiomyopathy
Publication date: Available online 22 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Jianqiang Hu, Shanjie Wang, Zhenyu Xiong, Zheng Cheng, Zhi Yang, Jie Lin, Tingting Wang, Xinyu Feng, Erhe Gao, Haichang Wang, Dongdong SunAbstractDiabetic cardiomyopathy (DCM) is characterized by cardiac microvascular endothelial cells (CMECs) injury and cardiomyocyte (CM) dysfunction. Exosomes mediated cellular communication between CMECs and CM has emerging roles in the pathogenesis of DCM, but the underlining mechanisms are unclear. Mammalian sterile 20-like kinase 1 (Mst1), a key component...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 23, 2018 Category: Molecular Biology Source Type: research

Editorial Board
Publication date: October 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 10Author(s): (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 23, 2018 Category: Molecular Biology Source Type: research

Ectopic expression of OX1R in ulcerative colitis mediates anti-inflammatory effect of orexin-A
Publication date: Available online 18 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): N. Messal, N. Fernandez, S. Dayot, V. Gratio, P. Nicole, C. Prochasson, I. Chantret, G. LeGuilloux, A. Jarry, A. Couvelard, X. Tréton, T. Voisin, E. Ogier-Denis, A. CouvineauAbstractOrexins (orexin-A and orexin-B) are hypothalamic peptides that are produced by the same precursor and are involved in sleep/wake control, which is mediated by two G protein-coupled receptor subtypes, OX1R and OX2R. Ulcerative colitis (UC) is an inflammatory bowel disease, (IBD) which is characterized by long...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 19, 2018 Category: Molecular Biology Source Type: research

Label-free FTIR spectroscopy detects and visualizes the early stage of pulmonary micrometastasis seeded from breast carcinoma
Publication date: Available online 18 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Karolina Chrabaszcz, Agnieszka Jasztal, Marta Smęda, Bartosz Zieliński, Aneta Blat, Max Diem, Stefan Chlopicki, Kamilla Malek, Katarzyna M. MarzecAbstractAn application of FTIR spectroscopic imaging for the identification and visualization of early micrometastasis from breast cancer to lungs in a murine model is shown. Spectroscopic and histological examination is focused on lung cross-sections derived from animals at the early phase of metastasis (early micrometastasis, EM) as compared to h...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 19, 2018 Category: Molecular Biology Source Type: research

Endothelial cell senescence in aging-related vascular dysfunction
This article is part of a Special Issue entitled: Genetic and epigenetic regulation of aging and longevity edited by Jun Ren & Megan Yingmei Zhang. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 18, 2018 Category: Molecular Biology Source Type: research

Autophagy mediates calcium-sensing receptor-induced TNFα production in human preadipocytes
We describe a novel mechanism and possible new target to modulate and prevent adipose inflammation and hence the resulting disease-generating adipose tissue dysfunction.Graphical abstract (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 18, 2018 Category: Molecular Biology Source Type: research

Reactive cysteine residues in the oxidative dimerization and Cu2+ induced aggregation of human γD-crystallin: Implications for age-related cataract
Publication date: Available online 18 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Srinivasagan Ramkumar, Xingjun Fan, Benlian Wang, Sichun Yang, Vincent M. MonnierAbstractCysteine (Cys) residues are major causes of crystallin disulfide formation and aggregation in aging and cataractous human lenses. We recently found that disulfide linkages are highly and partly conserved in β- and γ-crystallins, respectively, in human age-related nuclear cataract and glutathione depleted LEGSKO mouse lenses, and could be mimicked by in vitro oxidation. Here we determined which C...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 18, 2018 Category: Molecular Biology Source Type: research

Role of p38γ MAPK in regulation of EMT and cancer stem cells
Publication date: Available online 18 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Mei Xu, Siying Wang, Yongchao Wang, Huaxun Wu, Jacqueline A. Frank, Zhuo Zhang, Jia LuoAbstractp38γ is a member of p38 MAPK family which contains four isoforms p38α, p38β, p38γ, and p38δ. p38γ MAPK has unique function and is less investigated. Recent studies revealed that p38γ MAPK may be involved in tumorigenesis and cancer aggressiveness. However, the underlying cellular/molecular mechanisms remain unclear. Epithelial-mesenchymal transition (EMT) is a...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 18, 2018 Category: Molecular Biology Source Type: research

Galectin-1 attenuates cardiomyocyte hypertrophy through splice-variant specific modulation of CaV1.2 calcium channel
Publication date: Available online 16 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Jia Fan, Wenyong Fan, Jianzhen Lei, Yingying Zhou, Hongfei Xu, Isha Kapoor, Guoqing Zhu, Juejin WangAbstractPressure overload-induced cardiac hypertrophy occurs in response to chronic blood pressure increase, and dysfunction of CaV1.2 calcium channel involves in cardiac hypertrophic processes by perturbing intracellular calcium concentration ([Ca2+]i) and calcium-dependent signaling. As a carbohydrate-binding protein, galectin-1 (Gal-1) is found to bind with CaV1.2 channel, which regulates vas...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 16, 2018 Category: Molecular Biology Source Type: research

Inhibition of CYP2E1 attenuates myocardial dysfunction in a murine model of insulin resistance through NLRP3-mediated regulation of mitophagy
In conclusion, these data depict that insulin resistance through CYP2E1 may contribute to the pathogenesis of myopathic changes including myocardial contractile dysfunction, oxidative stress and mitochondrial injury, possibly through activation of iNOS and NLRP3 signaling. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 16, 2018 Category: Molecular Biology Source Type: research

Vascular smooth muscle cell senescence and age-related diseases: State of the art
Publication date: Available online 16 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Chen Chi, Dong-Jie Li, Yu-Jie Jiang, Jie Tong, Hui Fu, Yi-Hang Wu, Fu-Ming ShenAbstractAging is a worldwide challenge, and it is accompanied by the accumulation of senescent cells. Cellular senescence is traditionally defined as permanent cell growth arrest and currently includes the senescence-associated secretory phenotype (SASP). There are two main types of cellular senescence, including telomere-dependent replicative senescence and stress-induced premature senescence. The process of cellul...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 16, 2018 Category: Molecular Biology Source Type: research

Improved cognition, mild anxiety-like behavior and decreased motor performance in pyridoxal phosphatase-deficient mice
Publication date: Available online 16 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Elisabeth Jeanclos, Monique Albersen, Rúben J.J. Ramos, Annette Raab, Christian Wilhelm, Leif Hommers, Klaus-Peter Lesch, Nanda M. Verhoeven-Duif, Antje GohlaAbstractPyridoxal 5′-phosphate (PLP) is an essential cofactor in the catalysis of ~140 different enzymatic reactions. A pharmacological elevation of cellular PLP concentrations is of interest in neuropsychiatric diseases, but whole-body consequences of higher intracellular PLP levels are unknown. To address this question, we ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 16, 2018 Category: Molecular Biology Source Type: research

Differences in structure and function between human and murine tau
Publication date: Available online 12 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Félix Hernández, Raquel Cuadros, Ivanna Ollá, Carlos García, Isidre Ferrer, George Perry, Jesús AvilaAbstractThe main difference between the primary structures of human and mouse tau can be found at the N-terminal end of the protein. Residues 17 to 28 in human tau are not present in the mouse form of the molecule. Here we tested the capacity of these human tau residues to bind to specific proteins. Several proteins were observed to bind to these residues. Amo...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 12, 2018 Category: Molecular Biology Source Type: research

Chemical chaperone 4-phenylbutyric acid alleviates the aggregation of human familial pulmonary fibrosis-related mutant SP-A2 protein in part through effects on GRP78
Publication date: Available online 11 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Xu Jiang, Guodong Fang, Li Dong, Peifeng Jin, Lu Ding, Haizeng Zhang, Junming Fan, Sunzhong Mao, Xiaofang Fan, Yongsheng Gong, Yongyu WangAbstractG231V and F198S mutations in surfactant protein A2 are associated with familial pulmonary fibrosis. These mutations cause defects in dimer/trimer assembly, trafficking, and secretion, as well as cause mutant protein aggregation. We investigated the effects and mechanisms of chemical chaperones on the cellular and biochemical properties of mutant SP-A...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 11, 2018 Category: Molecular Biology Source Type: research

Cln3 function is linked to osmoregulation in a Dictyostelium model of Batten disease
Publication date: Available online 11 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Sabateeshan Mathavarajah, Meagan McLaren, Robert J. HuberAbstractMutations in CLN3 cause a juvenile form of neuronal ceroid lipofuscinosis (NCL), commonly known as Batten disease. Currently, there is no cure for NCL and the mechanisms underlying the disease are not well understood. In the social amoeba Dictyostelium discoideum, the CLN3 homolog, Cln3, localizes predominantly to the contractile vacuole (CV) system. This dynamic organelle functions in osmoregulation, and intriguingly, osmoregula...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 11, 2018 Category: Molecular Biology Source Type: research

Animal models of cholestasis: An update on inflammatory cholangiopathies
Publication date: Available online 11 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Valeria Mariotti, Massimiliano Cadamuro, Carlo Spirli, Romina Fiorotto, Mario Strazzabosco, Luca FabrisAbstractCholestasis is a frequent clinical condition initiating or complicating chronic liver diseases, particularly cholangiopathies, where the biliary epithelium is the primary target of the pathogenetic sequence. Until a few decades ago, understanding of cholestasis relied mostly on the experimental model of bile duct ligation in rodents. However, a simple model of biliary obstruction cann...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 11, 2018 Category: Molecular Biology Source Type: research

Animal models for hepatocellular carcinoma
Publication date: Available online 10 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Hui Emma Zhang, James M. Henderson, Mark D. GorrellAbstractHepatocellular carcinoma (HCC) represents ~90% of all cases of primary liver cancer and occurs predominantly in patients with underlying chronic liver disease and cirrhosis. Establishing appropriate animal models for HCC is required for basic and translational studies, especially the models that can recapitulate one of the human disease settings. Current animal models can be categorized as chemically-induced, genetically-engineered, xe...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 11, 2018 Category: Molecular Biology Source Type: research

Adiponectin inhibits hepatic stellate cell activation by targeting the PTEN/AKT pathway
Publication date: Available online 8 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Pradeep Kumar, Reben Raeman, Daniel M. Chopyk, Tekla Smith, Kiran Verma, Yunshan Liu, Frank A. AnaniaAbstractAdiponectin inhibits hepatic stellate cell (HSC) activation and subsequent development of liver fibrosis via multiple mechanisms. Phosphatase and tensin homolog deletion 10 (PTEN) plays a crucial role in suppression of HSC activation, but its regulation by adiponectin is not fully understood. Here, we investigated the effect of adiponectin on PTEN in LX-2 cells, a human cell line and exa...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 8, 2018 Category: Molecular Biology Source Type: research

Mechanisms underlying modulation of podocyte TRPC6 channels by suPAR: Role of NADPH oxidases and Src family tyrosine kinases
Publication date: Available online 8 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Eun Young Kim, Naghmeh Hassanzadeh Khayyat, Stuart E. DryerAbstractThe soluble urokinase receptor (suPAR) has been implicated in the pathogenesis of chronic kidney diseases (CKD) and may function as a circulating “permeability factor” driving primary focal and segmental glomerulosclerosis (FSGS). Here we examined the mechanisms whereby suPAR causes mobilization and increased activation of Ca2+-permeable TRPC6 channels, which are also implicated in FSGS. Treatment of immortalized mou...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 8, 2018 Category: Molecular Biology Source Type: research

Double knockout of Akt2 and AMPK predisposes cardiac aging without affecting lifespan: Role of autophagy and mitophagy
In conclusion, our data indicate that Akt2-AMPK double ablation predisposes cardiac aging possibly related to compromised autophagy and mitophagy. This article is part of a Special Issue entitled: Genetic and epigenetic regulation of aging and longevity edited by Jun Ren & Megan Yingmei Zhang. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 8, 2018 Category: Molecular Biology Source Type: research

Combined effects of aquaporin-4 and hypoxia produce age-related hydrocephalus
Publication date: Available online 8 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): José Luis Trillo-Contreras, Reposo Ramírez-Lorca, Laura Hiraldo-González, Ismael Sánchez-Gomar, Ana Galán-Cobo, Nela Suárez-Luna, Eva Sánchez de Rojas-de Pedro, Juan José Toledo-Aral, Javier Villadiego, Miriam EchevarríaAbstractAquaporin-4, present in ependymal cells, in glia limiting and abundantly in pericapillary astrocyte foot processes, and aquaporin-1, expressed in choroid plexus epithelial cells, play an important role in cer...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 8, 2018 Category: Molecular Biology Source Type: research

Deciphering OPA1 mutations pathogenicity by combined analysis of human, mouse and yeast cell models
Publication date: Available online 4 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Valentina Del Dotto, Mario Fogazza, Francesco Musiani, Alessandra Maresca, Serena J. Aleo, Leonardo Caporali, Chiara La Morgia, Cecilia Nolli, Tiziana Lodi, Paola Goffrini, David Chan, Valerio Carelli, Michela Rugolo, Enrico Baruffini, Claudia ZannaAbstractOPA1 is the major gene responsible for Dominant Optic Atrophy (DOA) and the syndromic form DOA “plus”. Over 370 OPA1 mutations have been identified so far, although their pathogenicity is not always clear. We have analyzed one nov...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 4, 2018 Category: Molecular Biology Source Type: research

Early calcium handling imbalance in pressure overload-induced heart failure with nearly normal left ventricular ejection fraction
Publication date: Available online 4 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Sarah Rouhana, Charlotte Farah, Jerome Roy, Amanda Finan, Glaucy Rodrigues de Araujo, Patrice Bideaux, Valérie Scheuermann, Youakim Saliba, Cyril Reboul, Olivier Cazorla, Franck Aimond, Sylvain Richard, Jérôme Thireau, Nassim FaresAbstractHeart failure with preserved ejection fraction (HFpEF) is a common clinical syndrome associated with high morbidity and mortality. Therapeutic options are limited due to a lack of knowledge of the pathology and its evolution. We investigate...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 4, 2018 Category: Molecular Biology Source Type: research

The chromatin remodeling protein BRG1 regulates APAP-induced liver injury by modulating CYP3A11 transcription in hepatocyte
We report that hepatocyte-specific deletion of Brg1 attenuated APAP induced liver injury in mice as evidenced by reduced plasma ALT and AST levels, decreased liver necrosis, amelioration of GSH depletion, and prolonged survival. Brg1 regulated APAP-induced liver injury likely by stimulating the transcription of Cyp3a11, a key cytochrome enzyme involved in APAP metabolism. Immunoprecipitation coupled with DNA affinity microarray identified hepatocyte nuclear factor 4 (HNF4) as a novel binding partner for Brg1. HNF4 recruited Brg1 to the Cyp3a11 promoter and formed a complex with Brg1 to trans-activate Cyp3a11. In contrast, ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 3, 2018 Category: Molecular Biology Source Type: research

Bile acids and glucocorticoid metabolism in health and disease
Publication date: Available online 3 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Verena Theiler-Schwetz, Alex Zaufel, Hansjörg Schlager, Barbara Obermayer-Pietsch, Peter Fickert, Gernot ZollnerAbstractGlucocorticoids are regulators of stress response essential for survival. Liver disease can alter this homeostatic mechanism in patients with liver cirrhosis – a finding that might mirror the controversially discussed condition of critical illness related corticosteroid insufficiency.Underlying mechanisms might be shared molecular pathways in both bile acid as well ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 3, 2018 Category: Molecular Biology Source Type: research

BRG1 regulates NOX gene transcription in endothelial cells and contributes to cardiac ischemia-reperfusion injury
In conclusion, our data suggest that BRG1 may link epigenetic activation of NOX transcription in endothelial cells to cardiac ischemia reperfusion injury. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 3, 2018 Category: Molecular Biology Source Type: research

Polycystin-1 downregulation induces ERK-dependent mTOR pathway activation in a cellular model of psoriasis
Publication date: Available online 2 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Antonios N. Gargalionis, Lina S. Malakou, Christos Adamopoulos, Christina Piperi, Irini Theochari, Marjan Nokhbehsaim, James Deschner, Georgios Kokkalis, Penelope Korkolopoulou, Evangelia Papadavid, Athanasios G. Papavassiliou, Efthimia K. BasdraAbstractPsoriatic plaques tend to localize to the knees and elbows, areas that are particularly subject to mechanical stress resulting from bending and friction. Moreover, plaques often develop at sites of mechanical trauma or injury (Koebner phenomenon...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 2, 2018 Category: Molecular Biology Source Type: research

Pigment epithelium derived factor regulates human Sost/Sclerostin and other osteocyte gene expression via the receptor and induction of Erk/GSK-3beta/beta-catenin signaling
We reported that PEDF suppressed expression of Sost/Sclerostin and other osteocyte related genes in mineralizing osteoblast cultures and suggested that this could be part of the mechanisms by which PEDF regulates matrix mineralization (Li et al. J Cellular Phys. 2014). We have used a long-term differentiated mineralizing osteoblast culture (LTD) to define mechanisms by which PEDF regulates osteocyte gene expression. LTD cultures were established by culturing human osteoblasts in an osteogenic medium for 4 months followed by analysis of osteocytes related genes and encoded proteins. LTD cells synthesized Sclerostin, matri...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 2, 2018 Category: Molecular Biology Source Type: research

Glucose-free/high-protein diet improves hepatomegaly and exercise intolerance in glycogen storage disease type III mice
Publication date: Available online 1 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Serena Pagliarani, Sabrina Lucchiari, Gianna Ulzi, Michela Ripolone, Raffaella Violano, Francesco Fortunato, Andreina Bordoni, Stefania Corti, Maurizio Moggio, Nereo Bresolin, Giacomo P. ComiAbstractGlycogen disease type III (GSDIII), a rare incurable autosomal recessive disorder due to glycogen debranching enzyme deficiency, presents with liver, heart and skeletal muscle impairment, hepatomegaly and ketotic hypoglycemia. Muscle weakness usually worsens to fixed myopathy and cardiac involvement...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 2, 2018 Category: Molecular Biology Source Type: research

NASP antagonize chromatin accessibility through maintaining histone H3K9me1 in hepatocellular carcinoma
Publication date: Available online 1 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Xuan Kang, Yun Feng, Zhixue Gan, Shiyang Zeng, Xiaobo Guo, Xirui Chen, Ye Zhang, Chen Wang, Kuinan Liu, Xuelin Chen, Xiaoxue Jiang, Shuting Song, Yabin Li, Su Chen, Feng Sun, Zhiyong Mao, Xiaomei Yang, Jianfeng ChangAbstractThe regulation of histone deposits mediated by multi-chaperone complexes under physiological conditions remains to be further investigated. Here, we studied the function of nuclear autoantigenic sperm protein (NASP) in the regulation of liver cancer. We found that NASP level...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 2, 2018 Category: Molecular Biology Source Type: research

Altered structure and function of fibrinogen after cleavage by Factor VII Activating Protease (FSAP)
In conclusion, altering fibrin clot properties by fibrinogenolysis is a novel function of FSAP in the vasculature, which facilitates clot lysis and may in vivo contribute to reduced fibrin deposition during thrombosis. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 2, 2018 Category: Molecular Biology Source Type: research

A novel porcupine inhibitor blocks WNT pathways and attenuates cardiac hypertrophy
Publication date: Available online 1 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Jiahui Jiang, Cong Lan, Liangpeng Li, Dezhong Yang, Xuewei Xia, Qiao Liao, Wenbin Fu, Xiongwen Chen, Songzhu An, Wei Eric Wang, Chunyu ZengAbstractWNT pathways are critically involved in the cardiac hypertrophy growth. Porcupine, an acyltransferase that specifically enables secretion of all WNT ligands, became a highly druggable target for inhibiting WNT pathways. Here we test if a novel small-molecule porcupine inhibitor CGX1321, which has entered human clinical trials as an anti-cancer agent,...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 2, 2018 Category: Molecular Biology Source Type: research

In vitro and in vivo translational models for rare liver diseases
Publication date: Available online 1 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Sharie J. Haugabook, Marc Ferrer, Elizabeth A. OttingerAbstractA challenge in developing effective treatments is the modeling of the human disease using in vitro and in vivo systems. Animal models have played a critical role in the understanding of disease pathophysiology, target validation, and evaluation of novel therapeutic agents. However, as the success rate from entry into clinical testing to drug approval remains low, it is critical to have high quality and well-validated models reflecti...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 2, 2018 Category: Molecular Biology Source Type: research

Pharmacological blockade of CXCR3 by (±)-NBI-74330 reduces neuropathic pain and enhances opioid effectiveness - Evidence from in vivo and in vitro studies
Publication date: Available online 1 August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Anna Piotrowska, Ewelina Rojewska, Katarzyna Pawlik, Grzegorz Kreiner, Agata Ciechanowska, Wioletta Makuch, Magdalena Zychowska, Joanna MikaAbstractIt has been suggested that CXCR3 is important for nociception. Our experiments were conducted to evaluate involvement of CXCR3 and its ligands (CXCL4, CXCL9, CXCL10, CXCL11/CCL21) in neuropathic pain. Our studies give new evidence that intrathecal administration of each CXCR3 ligand induces pain-like behaviour in naive mice that occurs shortly after...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - August 2, 2018 Category: Molecular Biology Source Type: research

Animal models for cystic fibrosis liver disease (CFLD)
Publication date: Available online 30 July 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Romina Fiorotto, Mariangela Amenduni, Valeria Mariotti, Massimiliano Cadamuro, Luca Fabris, Carlo Spirli, Mario StrazzaboscoAbstractLiver disease is a severe complication in patients with Cystic Fibrosis (CF), a genetic disease caused by mutations in the gene encoding for cystic fibrosis transmembrane conductance regulator (CFTR) channel. The sequence of events leading to CFLD is still unclear and has limited the development of more specific treatments other than the bile acid UDCA. However, in ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 30, 2018 Category: Molecular Biology Source Type: research

Senescence and declining reproductive potential: Insight into molecular mechanisms through testicular metabolomics
Publication date: Available online 29 July 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Ivana Jarak, Susana Almeida, Rui A. Carvalho, Mário Sousa, Alberto Barros, Marco G. Alves, Pedro F. OliveiraAbstractAging is associated with structural and functional changes in the organism that result in the declining of its functioning. Postponed parenthood has renewed the interest in age-related decline of testicular function and male fertility. Still, little is known about the molecular mechanisms associated with testicular senescence and related decline of fertility. Here we sought ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 29, 2018 Category: Molecular Biology Source Type: research

Editorial Board
Publication date: September 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 9, Part AAuthor(s): (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 27, 2018 Category: Molecular Biology Source Type: research

Editorial Board
Publication date: September 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 9, Part BAuthor(s): (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 26, 2018 Category: Molecular Biology Source Type: research

Aberrant cardiolipin metabolism is associated with cognitive deficiency and hippocampal alteration in tafazzin knockdown mice
Publication date: Available online 25 July 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Laura K. Cole, Jin Hee Kim, Andrew A. Amoscato, Yulia Y. Tyurina, Hülya Bayır, Benyamin Karimi, Tabrez J. Siddiqui, Valerian E. Kagan, Grant M. Hatch, Tiina M. KauppinenAbstractCardiolipin (CL) is a key mitochondrial phospholipid essential for mitochondrial energy production. CL is remodeled from monolysocardiolipin (MLCL) by the enzyme tafazzin (TAZ). Loss-of-function mutations in the gene which encodes TAZ results in a rare X-linked disorder called Barth Syndrome (BTHS). The mutated TAZ ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 26, 2018 Category: Molecular Biology Source Type: research

Animal models of portal hypertension
Publication date: Available online 25 July 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): P. Königshofer, K. Brusilovskaya, P. Schwabl, T. ReibergerAbstractChronic liver diseases ultimately lead to cirrhosis and portal hypertension (PHT). Indeed, PHT is a major cause for severe complications, while medical treatment is limited to non-selective betablockers. Sophisticated animal models are needed to investigate novel treatment options for different etiologies of liver disease, effective anti-fibrotic agents as well as vasoactive drugs against PHT. In this review, we present some ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 26, 2018 Category: Molecular Biology Source Type: research

Pparα-independent effects of nitrate supplementation on skeletal muscle metabolism in hypoxia
Publication date: Available online 25 July 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Katie A. O'Brien, James A. Horscroft, Jules Devaux, Ross T. Lindsay, Alice Strang Steel, Anna D. Clark, Andrew Philp, Stephen D.R. Harridge, Andrew J. MurrayAbstractHypoxia is a feature of many disease states where convective oxygen delivery is impaired, and is known to suppress oxidative metabolism. Acclimation to hypoxia thus requires metabolic remodelling, however hypoxia tolerance may be aided by dietary nitrate supplementation. Nitrate improves tissue oxygenation and has been shown to modul...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 25, 2018 Category: Molecular Biology Source Type: research

The von Hippel Lindau tumour suppressor gene is a novel target of E2F4-mediated transcriptional repression in preeclampsia
In conclusion, we demonstrate for the first time that hypomethylation of VHL DNA at a key transcription factor binding site has significant consequences for its transcriptional repression in early-onset preeclampsia.Graphical abstract (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 24, 2018 Category: Molecular Biology Source Type: research

Leptin restores markers of female fertility in lipodystrophy
Publication date: Available online 23 July 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Lisa Eifler, Annett Hoffmann, Isabel Viola Wagner, Nora Klöting, Lena Sahlin, Thomas Ebert, Beate Jessnitzer, Ulrike Lössner, Michael Stumvoll, Olle Söder, Mathias Fasshauer, Susan KralischAbstractObjectivesFemale reproductive dysfunction occurs in patients with pathological loss of adipose tissue, i.e. lipodystrophy (LD). However, mechanisms remain largely unclear and treatment effects of adipocyte-derived leptin have not been assessed in LD animals.MethodsIn the current study, C...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 24, 2018 Category: Molecular Biology Source Type: research

Exercise improves glucose uptake in murine myotubes through the AMPKα2-mediated induction of Sestrins
In this study, we aim to better understand the relationship between SESNs and AMPK in response to exercise training and the possible mechanism by which SESNs mediate glucose metabolism. We used wild type, AMPKα2+/− and AMPKα2−/− C57BL/6 mice to reveal the pathway by which 6 weeks of exercise training induced SESNs. We explored the mechanism through which SESNs regulated glucose metabolism in vitro by overexpressing or inhibiting SESNs, and inhibiting AMPK or autophagy in myotubes. We found that a 6-week exercise training regime improved oxidative metabolism, activated the insulin signaling p...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 23, 2018 Category: Molecular Biology Source Type: research

Adipose tissue derived-factors impaired pancreatic β-cell function in diabetes
Publication date: Available online 23 July 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Sandra A. Rebuffat, Emmanuelle Sidot, Caroline Guzman, Jacqueline Azay-Milhau, Bernard Jover, Anne-Dominique Lajoix, Sylvie Peraldi-RouxAbstractInflammatory factors produced and secreted by adipose tissue, in particular peri-pancreatic adipose tissue (P-WAT), may influence pancreatic β-cell dysfunction. Using the ZDF Rat model of diabetes, we show the presence of infiltrating macrophage (ED1 staining) on pancreatic tissue and P-WAT in the pre-diabetes stage of the disease. Then, when the T2...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 23, 2018 Category: Molecular Biology Source Type: research

Protective role of soluble adenylyl cyclase against reperfusion-induced injury of cardiac cells
ConclusionsAC plays an essential role in supporting cardiomyocytes viability during reperfusion. Elevation of mitochondrial cAMP pool either by sAC overexpression or PDE2 inhibition beneficially affects cardiomyocyte survival during reperfusion. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 23, 2018 Category: Molecular Biology Source Type: research

Cystathionine beta synthase-hydrogen sulfide system in paraventricular nucleus reduced high fatty diet induced obesity and insulin resistance by brain-adipose axis
In conclusion, leptin activates neuron CBS-H2S system by FOXO3a, regulates neuroendocrine hormones to modulate the energy homeostasis, thus highlights a new brain-adipose feedback axis in energy metabolism. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 21, 2018 Category: Molecular Biology Source Type: research

Proteomic identification of altered protein O-GlcNAcylation in a triple transgenic mouse model of Alzheimer's disease
Publication date: Available online 18 July 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Antonella Tramutola, Nidhi Sharma, Eugenio Barone, Chiara Lanzillotta, Andrea Castellani, Federica Iavarone, Federica Vincenzoni, Massimo Castagnola, D. Allan Butterfield, Silvana Gaetani, Tommaso Cassano, Marzia Perluigi, Fabio Di DomenicoAbstractPET scan analysis demonstrated the early reduction of cerebral glucose metabolism in Alzheimer disease (AD) patients that can make neurons vulnerable to damage via the alteration of the hexosamine biosynthetic pathway (HBP). Defective HBP leads to flaw...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 20, 2018 Category: Molecular Biology Source Type: research

LAZ3 protects cardiac remodeling in diabetic cardiomyopathy via regulating miR-21/PPARa signaling
In conclusion, LAZ3 protects against cardiac remodeling in DCM by decreasing miR-21, thus regulating PPARa/NRF2 signaling. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - July 20, 2018 Category: Molecular Biology Source Type: research