Long non-coding RNA cytoskeleton regulator RNA (CYTOR) modulates pathological cardiac hypertrophy through miR-155-mediated IKKi signaling
Publication date: Available online 19 February 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Yuan Yuan, Juan Wang, Qiuxiang Chen, Qingqing Wu, Wei Deng, Heng Zhou, Difei ShenAbstractPathological cardiac hypertrophy, which may lead to heart failure and sudden death, can be affected by multiple factors. In our previous study, we revealed that IKKi deficiency induced cardiac hypertrophy through the activation of the AKT and NF-kB signaling pathway in response to aortic banding (AB). Non-coding RNAs, mainly long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), play a crucial role in no...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - February 20, 2019 Category: Molecular Biology Source Type: research

Endothelial dysfunction in pregnancy metabolic disorders
Publication date: Available online 19 February 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Cesar Echeverria, Felipe Eltit, Juan F. Santibanez, Sebastian Gatica, Claudio Cabello-Verrugio, Felipe SimonAbstractIn recent years, the vascular endothelium has gained attention as a key player in the initiation and development of pregnancy disorders.Endothelium acts as an endocrine organ that preserves the homeostatic balance by responding to changes in metabolic status. However, in metabolic disorders, endothelial cells adopt a dysfunctional function, losing their normal responsiveness.Du...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - February 20, 2019 Category: Molecular Biology Source Type: research

Sequence- and seed-structure-dependent polymorphic fibrils of alpha-synuclein
In this study, we found that human and mouse a-syn aggregated in vitro formed morphologically distinct amyloid fibrils exhibiting twisted and straight structures, respectively. Furthermore, we identified different protease-resistant core regions, long and short, in human and mouse a-syn aggregates. Interestingly, among the seven unconserved amino acids, only A53T substitution, one of the familial PD mutations, was responsible for structural conversion to the straight-type. Finally, we checked whether the structural differences are transmissible by seeding and found that human a-syn seeded with A53T aggregates formed straig...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - February 19, 2019 Category: Molecular Biology Source Type: research

The power of metabolism — Linking energy supply and demand with cardiac contractile function
Publication date: Available online 18 February 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Michael Schwarzer, Torsten Doenst, Christine Des Rosiers, Jan F.C. Glatz (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - February 19, 2019 Category: Molecular Biology Source Type: research

Inhibition of PRMT3 activity reduces hepatic steatosis without altering atherosclerosis susceptibility in apoE knockout mice
Publication date: Available online 15 February 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Menno Hoekstra, Joya E. Nahon, Laura M. de Jong, Mara J. Kröner, Lidewij R. de Leeuw, Miranda Van EckAbstractThe nuclear receptor liver X receptor (LXR) impacts on cholesterol metabolism as well as hepatic lipogenesis via transcriptional regulation. It is proposed that inhibition of the protein arginine methyltransferase 3 (PRMT3) uncouples these two transcriptional pathways in vivo by acting as a specific lipogenic coactivator of LXR. Here we validated the hypothesis that treatment wit...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - February 16, 2019 Category: Molecular Biology Source Type: research

The potential contribution of stromal cell-derived factor 2 (SDF2) in endoplasmic reticulum stress response in severe preeclampsia and labor-onset
Publication date: Available online 15 February 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Aline R. Lorenzon-Ojea, Hong Wa Yung, Graham J. Burton, Estela BevilacquaAbstractEndoplasmic reticulum (ER) stress occurs when the protein folding machinery in the cell is unable to cope with newly synthesized proteins, which results in an accumulation of misfolded proteins in the ER lumen. In response, the cell activates a cellular signaling pathway known as the Unfolded Protein Response (UPR), aiming to restore cellular homeostasis. Activation and exacerbation of the UPR have been describe...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - February 16, 2019 Category: Molecular Biology Source Type: research

RhoC/ROCK2 promotes vasculogenic mimicry formation primarily through ERK/MMPs in hepatocellular carcinoma
Publication date: Available online 16 February 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Ji-Gang Zhang, Dan-Dan Zhang, Ying Liu, Juan-Ni Hu, Xue Zhang, Li Li, Wan Mu, Guan-Hua Zhu, Qin Li, Gao-Lin LiuAbstractVasculogenic mimicry (VM) results in the formation of an alternative circulatory system that can improve the blood supply to multiple malignant tumors, including hepatocellular carcinoma (HCC). However, the potential mechanisms of RhoC/ROCK in VM have not yet been investigated in HCC. Here, RhoC expression was upregulated in HCC tissues, especially the VM-positive (VM+) grou...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - February 16, 2019 Category: Molecular Biology Source Type: research

FMRpolyG alters mitochondrial transcripts level and respiratory chain complex assembly in Fragile X associated tremor/ataxia syndrome [FXTAS]
Publication date: Available online 13 February 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Dhruv Gohel, Lakshmi Sripada, Paresh Prajapati, Kritarth Singh, Milton Roy, Darshan Kotadia, Flora Tassone, Nicolas Charlet-Berguerand, Rajesh SinghAbstractFragile X-associated tremor/ataxia syndrome (FXTAS) is an inherited neurodegenerative disorder caused by an expansion of 55 to 200 CGG repeats (premutation) in FMR1. These CGG repeats are Repeat Associated non-ATG (RAN) translated into a small and pathogenic protein, FMRpolyG. The cellular and molecular mechanisms of FMRpolyG toxicity are...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - February 14, 2019 Category: Molecular Biology Source Type: research

SIRT1 participates in the response to methylglyoxal-dependent glycative stress in mouse oocytes and ovary
Publication date: Available online 13 February 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Giovanna Di Emidio, Silvano Junior Santini, Anna Maria D'Alessandro, Antonella Vetuschi, Roberta Sferra, Paolo Giovanni Artini, Gaspare Carta, Stefano Falone, Fernanda Amicarelli, Carla TatoneAbstractMethylglyoxal (MG), a highly reactive dicarbonyl derived from metabolic processes, is the most powerful precursor of advanced glycation end products (AGEs). Glycative stress has been recently associated with ovarian dysfunctions in aging and PCOS syndrome. We have investigated the role of the NA...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - February 14, 2019 Category: Molecular Biology Source Type: research

Two mechanisms involving the autophagic and proteasomal pathways process the metastasis suppressor protein, N-myc downstream regulated gene 1
Publication date: Available online 11 February 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Sumit Sahni, Kyung Chan Park, Zaklina Kovacevic, Des R. RichardsonAbstractN-myc downstream regulated gene 1 (NDRG1) is an intriguing metastasis suppressor protein, which plays an important role in suppressing multiple oncogenic signaling pathways. Interestingly, multiple isoforms of NDRG1 have been identified, although the molecular mechanisms involved in their generation remains elusive. Herein, we demonstrate the role of two mechanisms involving autophagic and proteasomal machinery as part...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - February 12, 2019 Category: Molecular Biology Source Type: research

Lysophosphatidic acid receptor 1 inhibitor, AM095, attenuates diabetic nephropathy in mice by downregulation of TLR4/NF-κB signaling and NADPH oxidase
In conclusion, AM095 is effective in preventing the pathogenesis of DN by inhibiting TLR4/NF-κB and the NADPH oxidase system, consequently inhibiting the inflammatory signaling cascade in renal tissue of diabetic mice, suggesting that LPAR1 antagonism might provide a potential therapeutic target for DN. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - February 12, 2019 Category: Molecular Biology Source Type: research

Generation of induced pluripotent stem cells using elastin like polypeptides as a non-viral gene delivery system
Publication date: Available online 10 February 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Chang Hyun Lee, Rohan S.J. Ingrole, Harvinder Singh GillAbstractInduced pluripotent stem cells (iPSCs) have been generated from various somatic cells using different approaches; however, a major restriction of reprogramming methods is the use of viral vectors, which have the risk of causing genome-integration of viral DNA. Here, without a viral vector, we generated iPSCs from mouse fibroblasts using an elastin-like polypeptide (ELP)-based transfection method. Our findings support the possibl...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - February 11, 2019 Category: Molecular Biology Source Type: research

Embryonic programming of heart disease in response to obesity during pregnancy
Publication date: Available online 10 February 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Abdalla Ahmed, Paul Delgado-OlguinAbstractObesity during pregnancy programs adult-onset heart disease in the offspring. Clinical studies indicate that exposure to an adverse environment in utero during early, as compared to late, gestation leads to a higher prevalence of adult-onset heart disease. This suggests that the early developing heart is particularly sensitive to an adverse environment. Accordingly, growing evidence from clinical studies and animal models demonstrates that obesity du...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - February 11, 2019 Category: Molecular Biology Source Type: research

Plausible biochemical mechanisms of chemotherapy-induced cognitive impairment (“chemobrain”), a condition that significantly impairs the quality of life of many cancer survivors
Publication date: Available online 10 February 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Xiaojia Ren, Diana Boriero, Luksana Chaiswing, Subbarao Bondada, Daret K. St. Clair, D. Allan ButterfieldAbstractIncreasing numbers of cancer patients survive and live longer than five years after therapy, but very often side effects of cancer treatment arise at same time. One of the side effects, chemotherapy-induced cognitive impairment (CICI), also called “chemobrain” or “chemofog” by patients, brings enormous challenges to cancer survivors following successful che...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - February 11, 2019 Category: Molecular Biology Source Type: research

Impact of apolipoprotein A1- or lecithin:cholesterol acyltransferase-deficiency on white adipose tissue metabolic activity and glucose homeostasis in mice
We report that universal deletion of apoa1 or lcat expression in mice fed western-type diet results in increased sensitivity to body-weight gain compared to control C57BL/6 group. These changes in mouse genome correlate with discrete effects on white adipose tissue (WAT) metabolic activation and plasma glucose homeostasis. Apoa1-deficiency results in reduced WAT mitochondrial non-shivering thermogenesis. Lcat-deficiency causes a concerted reduction in both WAT oxidative phosphorylation and non-shivering thermogenesis, rendering lcat−/− mice the most sensitive to weight gain out of the three strains tested, foll...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - February 10, 2019 Category: Molecular Biology Source Type: research

Treatment with celastrol protects against obesity through suppression of galanin-induced fat intake and activation of PGC-1α/GLUT4 axis-mediated glucose consumption
In conclusion, the weight-lowering effects of celastrol are driven by decreased galanin-induced food consumption. Thus, this study contributes to our understanding of the anti-obese role of celastrol, and provides a possibility of using celastrol to treat obesity in clinic. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - February 10, 2019 Category: Molecular Biology Source Type: research

Placental serotonin systems in pregnancy metabolic complications associated with maternal obesity and gestational diabetes mellitus
Publication date: Available online 7 February 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Padma Murthi, Cathy VaillancourtAbstractSerotonin (5-hydroxytryptamine, 5-HT) regulates diverse physiological and behavioural and processes, also acts as a developmental signal in early embryogenesis and in regulation of fetal development. A number of studies have implicated the prominent role of serotonin transporter (SERT or 5-HTT) and 5-HT receptor subtypes in placental development and function. Here, in this article we have provided a comprehensive review on the important role of 5-HT hom...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - February 8, 2019 Category: Molecular Biology Source Type: research

Hypothalamic expression of the atypical chemokine receptor ACKR2 is involved in the systemic regulation of glucose tolerance
The objective of the present study was identifying chemokines potentially involved in the development of hypothalamic diet-induced inflammation. In order to identify chemokines potentially involved in this process, we performed a real-time PCR array that determined Ackr2 as one of the transcripts undergoing differential regulation in obese-prone as compared to obese-resistant mice fed a high-fat diet for three days. ACKR2 is a decoy receptor that acts as an inhibitor of the signals generated by several CC inflammatory chemokines. Our results show that Ackr2 expression is rapidly induced after exposure to dietary fats both ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - February 7, 2019 Category: Molecular Biology Source Type: research

Chronic kidney disease induced by an adenine rich diet upregulates integrin linked kinase (ILK) and its depletion prevents the disease progression
Publication date: Available online 3 February 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Sergio de Frutos, Alicia Luengo, Andrea García Jérez, Marco Hatem Vaquero, Mercedes Griera, Francisco O'Valle, Manuel Rodríguez–Puyol, Diego Rodríguez–Puyol, Laura CallerosAbstractKidney fibrosis is one of the main pathological findings of progressive chronic kidney disease (CKD) although the pathogenesis of renal scar formation remains incompletely explained. Integrin-linked kinase (ILK), a major scaffold protein between the extracellular matrix (ECM) ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - February 3, 2019 Category: Molecular Biology Source Type: research

Extent of rescue of F508del-CFTR function by VX-809 and VX-770 in human nasal epithelial cells correlates with SNP rs7512462 in SLC26A9 gene in F508del/F508del Cystic Fibrosis patients
ConclusionThe CFTR function can be performed in F508del/F508del patient-derived CRC-HNEs and its function and responses to VX-809 + VX-770 combination as well as clinical data, are all associated with the rs7512462 variant, which partially sheds light on the generally inter-individual phenotypic variability and in personalized responses to CFTR modulator drugs. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - February 2, 2019 Category: Molecular Biology Source Type: research

Wnt/β-catenin regulates blood pressure and kidney injury in rats
Publication date: Available online 30 January 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Liangxiang Xiao, Bo Xu, Lili Zhou, Roderick J. Tan, Dong Zhou, Haiyan Fu, Aiqing Li, Fan Fan Hou, Youhua LiuAbstractActivation of the renin-angiotensin system (RAS) plays a pivotal role in mediating hypertension, chronic kidney and cardiovascular diseases. As Wnt/β-catenin regulates multiple RAS genes, we speculated that this developmental signaling pathway might also participate in blood pressure (BP) regulation. To test this, we utilized two rat models of experimental hypertension: chr...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 31, 2019 Category: Molecular Biology Source Type: research

Adenosine kinase and cardiovascular fetal programming in gestational diabetes mellitus
Publication date: Available online 27 January 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Luis Silva, Torsten Plösch, Fernando Toledo, Marijke M. Faas, Luis SobreviaAbstractGestational diabetes mellitus (GDM) is a detrimental condition for human pregnancy associated with endothelial dysfunction and endothelial inflammation in the fetoplacental vasculature and leads to increased cardio-metabolic risk in the offspring. In the fetoplacental vasculature, GDM is associated with altered adenosine metabolism. Adenosine is an important vasoactive molecule and is an intermediary and f...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 28, 2019 Category: Molecular Biology Source Type: research

Excitotoxicity, neuroinflammation and oxidant stress as molecular bases of epileptogenesis and epilepsy-derived neurodegeneration: The role of vitamin E
Publication date: Available online 28 January 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Patrizia Ambrogini, Pierangelo Torquato, Desirée Bartolini, Maria Cristina Albertini, Davide Lattanzi, Michael Di Palma, Rita Marinelli, Michele Betti, Andrea Minelli, Riccardo Cuppini, Francesco GalliAbstractGlutamate-mediated excitotoxicity, neuroinflammation, and oxidative stress are common underlying events in neurodegeneration. This “triad” of pathogenic events characterizes the neurobiology of epilepsy, leading to seizure-induced cell death, increased susceptibility t...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 28, 2019 Category: Molecular Biology Source Type: research

Editorial Board
Publication date: 1 March 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1865, Issue 3Author(s): (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 27, 2019 Category: Molecular Biology Source Type: research

Adipocyte MTERF4 regulates non-shivering adaptive thermogenesis and sympathetic-dependent glucose homeostasis
Publication date: Available online 26 January 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Anna Castillo, Maria Vilà, Inés Pedriza, Rosario Pardo, Yolanda Cámara, Edgar Martín, Daniel Beiroa, Javier Torres-Torronteras, Marta Oteo, Miguel A. Morcillo, Ramon Martí, Rafael Simó, Rubén Nogueiras, Josep A. VillenaAbstractIn humans, low brown adipose tissue (BAT) mass and activity have been associated with increased adiposity and fasting glucose levels, suggesting that defective BAT-dependent thermogenesis could contribute to the developme...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 26, 2019 Category: Molecular Biology Source Type: research

The impact of maternal obesity in pregnancy on placental glucocorticoid and macronutrient transport and metabolism
Publication date: Available online 23 January 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Emma C. Johns, Fiona C. Denison, Rebecca M. ReynoldsAbstractMaternal obesity is the most common metabolic disturbance in pregnancy affecting>1 in 5 women in some countries. Babies born to obese women are heavier with more adiposity at birth, and are vulnerable to obesity and metabolic disease across the lifespan suggesting offspring health is ‘programmed’ by fetal exposure to an obese intra-uterine environment. The placenta plays a major role in dictating the impact of maternal...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 24, 2019 Category: Molecular Biology Source Type: research

The nitrone spin trap 5,5‑dimethyl‑1‑pyrroline N‑oxide binds to toll-like receptor-2-TIR-BB-loop domain and dampens downstream inflammatory signaling
Publication date: Available online 23 January 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Marcos D. Muñoz, Lucas J. Gutierrez, Sandrine Delignat, Jules Russick, Sandra E. Gomez, Sebastien Lacroix-Desmazes, Daniel R. Enriz, Dario C. RamirezAbstractThe nitrone spin trap 5,5‑dimethyl‑1‑pyrroline N‑oxide (DMPO) dampens endotoxin-induced and TLR4-driven priming of macrophages, but the mechanism remains unknown. The available information suggests a direct binding of DMPO to the TIR domain, which is shared between TLRs. However, TLR2-TIR domain is the only TLR that have be...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 24, 2019 Category: Molecular Biology Source Type: research

Complex, coordinated and highly regulated changes in placental signaling and nutrient transport capacity in IUGR
Publication date: Available online 23 January 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Stephanie Chassen, Thomas JanssonAbstractThe most common cause of intrauterine growth restriction (IUGR) in the developed world is placental insufficiency, a concept often used synonymously with reduced utero-placental and umbilical blood flows. However, placental insufficiency and IUGR are associated with complex, coordinated and highly regulated changes in placental signaling and nutrient transport including inhibition of insulin and mTOR signaling and down-regulation of specific amino acid...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 24, 2019 Category: Molecular Biology Source Type: research

Dystrophic mdx mouse myoblasts exhibit elevated ATP/UTP-evoked metabotropic purinergic responses and alterations in calcium signalling
In conclusion, whereas specificity of dystrophic myoblast excitation by extracellular nucleotides is determined by particular receptor overexpression, the intensity of such altered response depends on relative activities of downstream calcium regulators that are also affected by Dmd mutations. Furthermore, these phenotypic effects of DMD emerge as early as in undifferentiated muscle. Therefore, the pathogenesis of DMD and the relevance of current therapeutic approaches may need re-evaluation. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 24, 2019 Category: Molecular Biology Source Type: research

Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency
Publication date: Available online 22 January 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Kathrin Heuberger, Henry J. Bailey, Patricie Burda, Apirat Chaikuad, Ewelina Krysztofinska, Terttu Suormala, Céline Bürer, Seraina Lutz, Brian Fowler, D. Sean Froese, Wyatt W. Yue, Matthias R. BaumgartnerAbstractHuman methylmalonyl-CoA epimerase (MCEE) catalyzes the interconversion of d-methylmalonyl-CoA and l-methylmalonyl-CoA in propionate catabolism. Autosomal recessive pathogenic variations in MCEE reportedly cause methylmalonic aciduria (MMAuria) in eleven patients. We invest...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 23, 2019 Category: Molecular Biology Source Type: research

Knockout of Nr2e3 prevents rod photoreceptor differentiation and leads to selective L-/M-cone photoreceptor degeneration in zebrafish
Publication date: Available online 23 January 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Shanglun Xie, Shanshan Han, Zhen Qu, Fei Liu, Jingzhen Li, Shanshan Yu, James Reilly, Jiayi Tu, Xiliang Liu, Zhaojing Lu, Xuebin Hu, Tinsae Assefa Yimer, Yayun Qin, Yuwen Huang, Yuexia Lv, Tao Jiang, Xinhua Shu, Zhaohui Tang, Haibo Jia, Fulton WongAbstractMutations in the photoreceptor cell-specific nuclear receptor gene Nr2e3 increased the number of S-cone photoreceptors in human and murine retinas and led to retinal degeneration that involved photoreceptor and non-photoreceptor cells. The m...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 23, 2019 Category: Molecular Biology Source Type: research

Fibroblast growth factor 21 protects the heart from angiotensin II-induced cardiac hypertrophy and dysfunction via SIRT1
ConclusionsFGF21 improves cardiac function and alleviates Ang II-induced cardiac hypertrophy in a SIRT1-dependent manner. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 22, 2019 Category: Molecular Biology Source Type: research

Nrf2 deficiency aggravates Angiotensin II-induced cardiac injury by increasing hypertrophy and enhancing IL-6/STAT3-dependent inflammation
ConclusionOur results show that Nrf2 is important for the protection of the heart against Ang II-induced cardiac hypertrophy and inflammation by mechanisms involving the regulation of IL-6/STAT3-dependent signaling.Graphical abstractSchematic diagram showing the role of Nrf2 in cardiomyocytes during Ang II-induced Injury. Ang II up-regulates the expression of Nrf2, which in turn facilitates the transcription of genes associated with anti-oxidative stress, including SOD, HO-1, NQO-1 etc., and inhibits MEF2A transcription, which plays key roles during cardiac hypertrophy. Moreover, Ang II also promotes the secretion of IL-6,...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 20, 2019 Category: Molecular Biology Source Type: research

Downregulated lncRNA-MIAT confers protection against erectile dysfunction by downregulating lipoprotein lipase via activation of miR-328a-5p in diabetic rats
In this study, we aimed to investigate how lncRNA-MIAT affects ED in diabetes and the involved mechanism. Microarray analysis was performed to screen ED-related differentially expressed genes, regulatory microRNA (miR) and long noncoding RNA (lncRNA). Highly expressed lipoprotein lipase (LPL) was identified, and subsequently miR-328a-5p and lncRNA-MIAT were determined. Diabetes was induced by streptozotocin in rats, and diabetic rats with ED were selected. Vascular smooth muscle cells (VSMCs) and vascular endothelial cells (VECs) were cocultured. The siRNA against lncRNA-MIAT, miR-328a-5p mimic and overexpression vector of...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 18, 2019 Category: Molecular Biology Source Type: research

Role of insulin, adenosine, and adipokine receptors in the foetoplacental vascular dysfunction in gestational diabetes mellitus
This article is part of a Special Issue entitled: Membrane Transporters and Receptors in Pregnancy Metabolic Complications edited by Luis Sobrevia.Graphical abstract (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 18, 2019 Category: Molecular Biology Source Type: research

Sphingosine-1-phosphate promotes barrier-stabilizing effects in human microvascular endothelial cells via AMPK-dependent mechanisms
Publication date: Available online 17 January 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Sophie Dennhardt, Karl R. Finke, Andrea Huwiler, Sina M. ColdeweyAbstractBreakdown of the endothelial barrier is a critical step in the development of organ failure in severe inflammatory conditions such as sepsis. Endothelial cells from different tissues show phenotypic variations which are often neglected in endothelial research. Sphingosine-1-phosphate (S1P) and AMP-dependent kinase (AMPK) have been shown to protect the endothelium and phosphorylation of AMPK by S1P was shown in several ce...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 18, 2019 Category: Molecular Biology Source Type: research

Is there an effect of ischemic conditioning on myocardial contractile function following acute myocardial ischemia/reperfusion injury?
This article is part of a Special Issue entitled: The power of metabolism: Linking energy supply and demand to contractile function edited by Torsten Doenst, Michael Schwarzer and Christine Des Rosiers. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 18, 2019 Category: Molecular Biology Source Type: research

Epstein–Barr virus noncoding RNAs from the extracellular vesicles of nasopharyngeal carcinoma (NPC) cells promote angiogenesis via TLR3/RIG-I-mediated VCAM-1 expression
Publication date: Available online 16 January 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Shiyue Cheng, Zhi Li, Junju He, Shujun Fu, Yumei Duan, Qin Zhou, Yuanliang Yan, Xiaoyu Liu, Liyu Liu, Chang Feng, Lu Zhang, Jiang He, Yuezhen Deng, Lun-Quan SunAbstractViral noncoding RNAs (Epstein–Barr virus-encoded RNAs, EBERs) are believed to play a critical role in the progression of lymphoma and nasopharyngeal carcinoma (NPC). However, the accurate mechanisms accounting for their oncogenic function have not been elucidated, especially in terms of interaction between tumor cells and...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 17, 2019 Category: Molecular Biology Source Type: research

The damage-associated molecular pattern HMGB1 is released early after clinical hepatic ischemia/reperfusion
ConclusionHMGB1 seems the most pertinent DAMP in clinical hepatic I/R injury. Neutralizing mitochondrial oxidative stress may limit DAMP release after hepatic I/R and reduce liver damage. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 16, 2019 Category: Molecular Biology Source Type: research

Glaucocalyxin A-induced oxidative stress inhibits the activation of STAT3 signaling pathway and suppresses osteosarcoma progression in vitro and in vivo
Publication date: Available online 16 January 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Min Mao, Tao Zhang, Zhuoying Wang, Hongsheng Wang, Jing Xu, Fei Yin, Gangyang Wang, Mengxiong Sun, Zongyi Wang, Yingqi Hua, Zhengdong CaiAbstractOsteosarcoma (OS) is ranked as the most common primary bone malignancy in children and adolescents worldwide, and the 5-year overall survival rate of OS is not optimistic. Constitutive activation of signal transducer and activator of transcription 3 (STAT3) has been implicated in tumor cell growth, proliferation, and anti-apoptosis in OS. Therefore, ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 16, 2019 Category: Molecular Biology Source Type: research

Deficiency of perforin and hCNT1, a novel inborn error of pyrimidine metabolism, associated with a rapidly developing lethal phenotype due to multi-organ failure
Publication date: Available online 15 January 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Sandra Pérez-Torras, Aida Mata-Ventosa, Britt Drögemöller, Maja Tarailo-Graovac, Judith Meijer, Rutger Meinsma, Arno G. van Cruchten, Wim Kulik, Albert Viel-Oliva, Axel Bidon-Chanal, Colin J. Ross, Wyeth W. Wassermann, Clara D.M. van Karnebeek, Marçal Pastor-Anglada, André B.P. van KuilenburgAbstractPyrimidine nucleotides are essential for a vast number of cellular processes and dysregulation of pyrimidine metabolism has been associated with a variety of clinica...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 15, 2019 Category: Molecular Biology Source Type: research

Deficiency of mouse mast cell protease 4 mitigates cardiac dysfunctions in mice after myocardium infarction
This study tested a direct role of mMCP4 in mouse post-MI cardiac dysfunction and myocardial remodeling. Immunoblot and immunofluorescent double staining demonstrated mMCP4 expression in cardiomyocytes from the infarct zone from mouse heart at 28 day post-MI. At this time point, mMCP4-deficient Mcpt4−/− mice showed no difference in survival from wild-type (WT) control mice, yet demonstrated smaller infarct size, improved cardiac functions, reduced macrophage content but increased T-cell accumulation in the infarct region compared with those of WT littermates. mMCP4-deficiency also reduced cardiomyocyte apopto...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 12, 2019 Category: Molecular Biology Source Type: research

Tissue plasminogen activator and neuropathy open the blood-nerve barrier with upregulation of microRNA-155-5p in male rats
Publication date: Available online 6 January 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Ann-Kristin Reinhold, Shaobing Yang, Jeremy Tsung-Chieh Chen, Liu Hu, Reine-Solange Sauer, Susanne M. Krug, Egle M. Mambretti, Michael Fromm, Alexander Brack, Heike L. RittnerAbstractThe blood-nerve barrier (BNB) consisting of the perineurium and endoneurial vessels is sealed by tight junction proteins. BNB alterations are a crucial factor in the pathogenesis of peripheral neuropathies. However, barrier opening, e.g. by tissue plasminogen activator (tPA), can also facilitate topical applicatio...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 6, 2019 Category: Molecular Biology Source Type: research

Deficiency of metabolite sensing receptor HCA2 impairs the salutary effect of niacin in hemorrhagic shock
In conclusion, we report that Gpr109a-dependent signalling is important in restoring cellular energetics and immunometabolism following hemorrhagic shock. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 6, 2019 Category: Molecular Biology Source Type: research

Nanobody interaction unveils structure, dynamics and proteotoxicity of the Finnish-type amyloidogenic gelsolin variant
Publication date: Available online 6 January 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Toni Giorgino, Davide Mattioni, Amal Hassan, Mario Milani, Eloise Mastrangelo, Alberto Barbiroli, Adriaan Verhelle, Jan Gettemans, Maria Monica Barzago, Luisa Diomede, Matteo de RosaAbstractAGel amyloidosis, formerly known as familial amyloidosis of the Finnish-type, is caused by pathological aggregation of proteolytic fragments of plasma gelsolin. So far, four mutations in the gelsolin gene have been reported as responsible for the disease. Although D187N is the first identified variant and t...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 6, 2019 Category: Molecular Biology Source Type: research

Impact of advanced glycation end products (AGEs) signaling in coronary artery disease
Publication date: Available online 3 January 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Marinos Kosmopoulos, Dimitrios Drekolias, Phaedon D. Zavras, Christina Piperi, Athanasios G. PapavassiliouAbstractCoronary artery disease remains the leading cause of mortality in adult diabetic population with however, a high predominance also in non-diabetic subjects. In search of common molecular mechanisms and metabolic by-products with potential pathogenic role, increased advanced glycation end products (AGEs) present a critical biomarker for CAD development in both cases. Interaction of ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 4, 2019 Category: Molecular Biology Source Type: research

The HCM-causing Y235S cMyBPC mutation accelerates contractile function by altering C1 domain structure
In this study, we characterized the functional and structural effects of the HCM-causing Y235S mutation by performing mechanical experiments and molecular dynamics simulations (MDS). cMyBPC null mouse myocardium was virally transfected with wild-type (WT) or Y235S cMyBPC (KOY235S). We found that Y235S cMyBPC was properly expressed and incorporated into the cardiac sarcomere, suggesting that the mechanism of disease of the Y235S mutation is not haploinsufficiency or poison peptides. Mechanical experiments in detergent-skinned myocardium isolated from KOY235S hearts revealed hypercontractile behavior compared to KOWT hearts,...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 4, 2019 Category: Molecular Biology Source Type: research

Adenosine receptors as a new target for resveratrol-mediated glioprotection
Publication date: Available online 3 January 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Larissa Daniele Bobermin, Ricardo Haack Amaral Roppa, André Quincozes-SantosAbstractResveratrol, a natural polyphenolic compound, has been studied as a neuroprotective molecule. Our group has demonstrated that such effect is closely associated with modulation of glial functionality, but the underlying mechanisms are not fully understood. Because astrocytes actively participate in the brain inflammatory response, and activation of adenosine receptors can attenuate inflammatory processes,...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 4, 2019 Category: Molecular Biology Source Type: research

Down-regulated expression of LINC00518 prevents epithelial cell growth and metastasis in breast cancer through the inhibition of CDX2 methylation and activation of the Wnt signaling pathway
In conclusion, our findings revealed that down-regulation of LINC00518 might have the ability to suppress BC progression by up-regulating CDX2 expression through the reduction of methylation and blockade of the Wnt signaling pathway, resulting in the inhibition of proliferation and promotion of apoptosis of BC epithelial cells. (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 4, 2019 Category: Molecular Biology Source Type: research

The LMTK-family of kinases: Emerging important players in cell physiology and disease pathogenesis
Publication date: Available online 29 December 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Franz WendlerAbstractLemur Tail (former tyrosine) Kinases (LMTKs) comprise a novel family of regulated serine/threonine specific kinases with three structurally and evolutionary related members. LMTKs exercise a confusing variety of cytosolic functions in cell signalling and membrane trafficking. Moreover, LMTK2 and LMTK3 also reside in the nucleus where they participate in gene transcription/regulation. As a consequence, LMTKs impact cell proliferation and apoptosis, cell growth and differe...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - December 30, 2018 Category: Molecular Biology Source Type: research