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Biochimica et Biophysica Acta

Ingrid Kjos, Katharina Vestre, Noemi Antonella Guadagno, Marita Borg Distefano, Cinzia Progida
The intracellular movement and positioning of organelles and vesicles is mediated by the cytoskeleton and molecular motors. Small GTPases like Rab and Arf proteins are main regulators of intracellular transport by connecting membranes to cytoskeleton motors or adaptors. However, it is becoming clear that interactions between these small GTPases and the cytoskeleton are important not only for the regulation of membrane transport. In this review, we will cover our current understanding of the mechanisms underlying the connection between Rab and Arf GTPases and the cytoskeleton, with special emphasis on the double role of these interactions, not only in membrane trafficking but also in membrane and cytoskeleton remodeling...
July 15, 2018: Biochimica et Biophysica Acta
Lisa Eifler, Annett Hoffmann, Isabel Viola Wagner, Nora Klöting, Lena Sahlin, Thomas Ebert, Beate Jessnitzer, Ulrike Lössner, Michael Stumvoll, Olle Söder, Mathias Fasshauer, Susan Kralisch
OBJECTIVES: Female 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. METHODS: In the current study, C57Bl/6 LD mice on a low-density lipoprotein receptor knockout background were treated with leptin or saline for 8 weeks and compared to non-LD controls. RESULTS: The number of pups born was 37% lower in breeding pairs consisting of LD female mice x non-LD male mice (n = 3...
July 15, 2018: Biochimica et Biophysica Acta
C Muñoz-Flores, A Astuya, F J Roa, A Romero, J Acosta, O Sánchez, J R Toledo
No abstract text is available yet for this article.
July 14, 2018: Biochimica et Biophysica Acta
Xin-Mei Huo, Li-Feng Meng, Tao Jiang, Ming Li, Fang-Zhen Sun, Bo Sun, Jian-Ke Li
Fertilization requires decondensation of promatine-condensed sperm chromatin, a dynamic process serving as an attractive system for the study of chromatin reprogramming. Nucleoplasmin is a key factor in regulating nucleosome assembly as a chaperone during fertilization process. However, knowledge on nucleoplasmin in chromatin formation remains elusive. Herein, magnetic tweezers (MT) and a chromatin assembly system were used to study the nucleoplasmin-mediated DNA decondensation/condensation at the single-molecular level in vitro...
July 13, 2018: Biochimica et Biophysica Acta
Jinlong Wang, Xiuyuan Zhang, Jiming Ling, Yun Wang, Xiaolin Xu, Yuchen Liu, Chaozhi Jin, Jiyu Ju, Yanzhi Yuan, Fuchu He, Chunling Zhao, Jian Wang, Chunyan Tian
KRAB-containing zinc finger proteins (KZNF) constitute the largest family of transcriptional regulators in humans and play critical roles in normal development and tumorigenesis. However, the function and mechanism of most KZNFs remain unclear. Here, we report that ZNF496, a KZNF family member, interacts with the DNA binding domain (DBD) of estrogen receptor alpha (ERα) via its C2H2 domain. This interaction decreases ERα binding to chromatin DNA and results in the repression of ERα transactivation, the selective suppression of ERα target genes, and ultimately in a reduction of ERα-positive cell growth in the presence of E2...
July 13, 2018: Biochimica et Biophysica Acta
Bożena Bruhn-Olszewska, Vadim Molodtsov, Michał Sobala, Maciej Dylewski, Katsuhiko S Murakami, Michael Cashel, Katarzyna Potrykus
Precise regulation of gene expression is crucial for bacteria to respond to changing environmental conditions. In addition to protein factors affecting RNA polymerase (RNAP) activity, second messengers play an important role in transcription regulation, such as well-known effectors of the stringent response: guanosine 5'triphosphate-3'diphosphate and guanosine 3', 5'-bis(diphosphate) [(p)ppGpp]. Although much is known about importance of the 5' and 3' moieties of (p)ppGpp, the role of the guanine base remains somewhat cryptic...
July 13, 2018: Biochimica et Biophysica Acta
Michael S Dahabieh, Erminia Di Pietro, Maïka Jangal, Christophe Goncalves, Michael Witcher, Nancy E Braverman, Sonia V Del Rincón
Cancer is irrevocably linked to aberrant metabolic processes. While once considered a vestigial organelle, we now know that peroxisomes play a central role in the metabolism of reactive oxygen species, bile acids, ether phospholipids (e.g. plasmalogens), very-long chain, and branched-chain fatty acids. Immune system evasion is a hallmark of cancer, and peroxisomes have an emerging role in the regulation of cellular immune responses. Investigations of individual peroxisome proteins and metabolites support their pro-tumorigenic functions...
July 13, 2018: Biochimica et Biophysica Acta
Dániel Horváth, Adrienn Sipos, Evelin Major, Zoltán Kónya, Róbert Bátori, Dóra Dedinszki, Attila Szöllősi, István Tamás, Judit Iván, Andrea Kiss, Ferenc Erdődi, Beáta Lontay
Wound healing is a complex sequence of cellular and molecular processes such as inflammation, cell migration, proliferation and differentiation. ROCK is a widely investigated Ser/Thr kinase with important roles in rearranging the actomyosin cytoskeleton. ROCK inhibitors have already been approved to improve corneal endothelial wound healing. The purpose of this study was to investigate the functions of myosin phosphatase (MP or PPP1CB), a type-1 phospho-Ser/Thr-specific protein phosphatase (PP1), one of the counter enzymes of ROCK, in skin homeostasis and wound healing...
July 12, 2018: Biochimica et Biophysica Acta
Fengjiao Zheng, Jingnan Han, Haocheng Lu, Changting Cui, Jichun Yang, Qinghua Cui, Jun Cai, Yong Zhou, Chaoshu Tang, Guoheng Xu, Bin Geng
Hydrogen sulfide (H2S) is an essential neuromodulator, generates by cystathionine β synthase (CBS) or 3-mecaptopyruvate sulfurtransferase (3MST) in the brain. H2S can mediate paraventricular nucleus (PVN) neuron activity, and regulate neuroendocrine hormones secretion. On the other hand, CBS deficiency caused metabolic disorder and body weight reduction. However, whether CBS/H2S of PVN regulates neuroendocrine hormones to mediate energy metabolism is unknown. Here, we first identified the CBS co-localization with thyrotropin-releasing hormone (TRH) and corticotropin releasing hormone (CRH) positive neurons...
July 12, 2018: Biochimica et Biophysica Acta
Alma M Astudillo, María A Balboa, Jesús Balsinde
Phospholipase A2 s are enzymes that hydrolyze the fatty acid at the sn-2 position of the glycerol backbone of membrane glycerophospholipids. Given the asymmetric distribution of fatty acids within phospholipids, where saturated fatty acids tend to be present at the sn-1 position, and polyunsaturated fatty acids such as those of the omega-3 and omega-6 series overwhelmingly localize in the sn-2 position, the phospholipase A2 reaction is of utmost importance as a regulatory checkpoint for the mobilization of these fatty acids and the subsequent synthesis of proinflammatory omega-6-derived eicosanoids on one hand, and omega-3-derived specialized pro-resolving mediators on the other...
July 12, 2018: Biochimica et Biophysica Acta
Stefanie Nowak, Antonella Di Pizio, Anat Levit, Masha Y Niv, Wolfgang Meyerhof, Maik Behrens
BACKGROUND: In humans, bitterness perception is mediated by ~25 bitter taste receptors present in the oral cavity. Among these receptors three, TAS2R10, TAS2R14 and TAS2R46, exhibit extraordinary wide agonist profiles and hence contribute disproportionally high to the perception of bitterness. Perhaps the most broadly tuned receptor is the TAS2R14, which may represent, because of its prominent expression in extraoral tissues, a receptor of particular importance for the physiological actions of bitter compounds beyond taste...
July 12, 2018: Biochimica et Biophysica Acta
Liwei Wang, David I Yule
Ion channels are pore-forming protein complexes in membranes that play essential roles in a diverse array of biological activities. Ion channel activity is strictly regulated at multiple levels and by numerous cellular events to selectively activate downstream effectors involved in specific biological activities. For example, ions, binding proteins, nucleotides, phosphorylation, the redox state, channel subunit composition have all been shown to regulate channel activity and subsequently allow channels to participate in distinct cellular events...
July 12, 2018: Biochimica et Biophysica Acta
Graham Taylor, Mary-Anne Nguyen, Subhadeep Koner, Eric Freeman, C Patrick Collier, Stephen A Sarles
The droplet interface bilayer (DIB) method offers simple control over initial leaflet compositions in model membranes, enabling an experimental path to filling gaps in our knowledge about the interplay between compositional lipid asymmetry, membrane properties, and the behaviors of membrane-active species. Yet, the stability of lipid leaflet asymmetry in DIBs has received very little attention, particularly in the presence of peptides and ion channels that are often studied in DIBs. Herein, we demonstrate for the first time parallel, capacitance-based measurements of intramembrane potential with arrays of asymmetric DIBs assembled in a microfluidic device to characterize the stability of leaflet asymmetry over many hours in the presence and absence of membrane-active peptides...
July 10, 2018: Biochimica et Biophysica Acta
Shasha Liu, Juntao Yuan, Wenhui Yue, Yanwei Bi, Xiyue Shen, Junlin Gao, Xin Xu, Zhongbing Lu
Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid deposition and oxidative stress. It has been demonstrated that general control nonderepressible 2 (GCN2) is required to maintain hepatic fatty acid homeostasis under conditions of amino acid deprivation. However, the impact of GCN2 on the development of NAFLD has not been investigated. In this study, we used Gcn2-/- mice to investigate the effect of GCN2 on high fat diet (HFD)-induced hepatic steatosis. After HFD feeding for 12 weeks, Gcn2-/- mice were less obese than wild-type (WT) mice, and Gcn2-/- significantly attenuated HFD-induced liver dysfunction, hepatic steatosis and insulin resistance...
July 10, 2018: Biochimica et Biophysica Acta
Roberto Villalobos-Labra, PabloJ Sáez, Mario Subiabre, Luis Silva, Fernando Toledo, Francisco Westermeier, Fabián Pardo, Marcelo Farías, Luis Sobrevia
Obesity associates with the endoplasmic reticulum (ER) stress-induced endothelial dysfunction. Pregnant women with pre-pregnancy maternal obesity (PGMO) may transfer this potential risk to their offspring; however, whether ER stress occurs and associates with foetoplacental endothelial dysfunction in PGMO is unknown. We studied the l-arginine transport and nitric oxide (NO) synthesis in human umbilical vein endothelial cells (HUVECs) from women with PGMO or with a normal pre-pregnancy weight. We analysed the expression and activation of the ER stress sensors protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1α (IRE1α), and activating transcription factor 6 (ATF6)...
July 10, 2018: Biochimica et Biophysica Acta
José Santiago Ibañez-Cabellos, Carmen Aguado, Daniel Pérez-Cremades, José Luis García-Giménez, Carlos Bueno-Betí, Eva M García-López, Carlos Romá-Mateo, Susana Novella, Carlos Hermenegildo, Federico V Pallardó
Circulating histones have been proposed as targets for therapy in sepsis and hyperinflammatory symptoms. However, the proposed strategies have failed in clinical trials. Although different mechanisms for histone-related cytotoxicity are being explored, those mediated by circulating histones are not fully understood. Extracellular histones induce endothelial cell death, thereby contributing to the pathogenesis of complex diseases such as sepsis and septic shock. Therefore, the comprehension of cellular responses triggered by histones is capital to design effective therapeutic strategies...
July 10, 2018: Biochimica et Biophysica Acta
Domenico Cieri, Mattia Vicario, Francesca Vallese, Beatrice D'Orsi, Paola Berto, Alessandro Grinzato, Cristina Catoni, Diego De Stefani, Rosario Rizzuto, Marisa Brini, Tito Calì
Intracellular neurofibrillary tangles (NFT) composed by tau and extracellular amyloid beta (Aβ) plaques accumulate in Alzheimer's disease (AD) and contribute to neuronal dysfunction. Mitochondrial dysfunction and neurodegeneration are increasingly considered two faces of the same coin and an early pathological event in AD. Compelling evidence indicates that tau and mitochondria are closely linked and suggests that tau-dependent modulation of mitochondrial functions might be a trigger for the neurodegeneration process; however, whether this occurs either directly or indirectly is not clear...
July 10, 2018: Biochimica et Biophysica Acta
Jung Hwa Lim, Hyun Mi Kang, Hong-Ryul Jung, Dae-Soo Kim, Kyung Hee Noh, Chang Tae Kyung, Byoung Joon Kim, Duk Hyun Sung, Hyun-Soo Cho, Kyung-Sook Chung, Nam-Soon Kim, Cho-Rok Jung
The spastin protein (SPAST) contains an ATPase with diverse cellular activities (AAA) domain and regulates microtubule dynamics. Missense mutations of the SPAST gene are frequently detected in patients with hereditary spastic paraplegias (HSPs) and represent the main reason of loss of SPAST function; however, the pathogenicity of mutant SPAST is heterogeneous. Here, SPAST variant with an I344K mutation (I344K-SPAST) was identified in a Korean family with autosomal dominant-type HSP. We investigated the role of the I344K-SPAST in HSP to provide a therapeutic mechanism...
July 10, 2018: Biochimica et Biophysica Acta
Nikita A Mitkin, Alisa M Muratova, Kirill V Korneev, Vsevolod V Pavshintsev, Konstantin A Rumyantsev, Murad S Vagida, Aksinya N Uvarova, Marina A Afanasyeva, Anton M Schwartz, Dmitry V Kuprash
CD58 is expressed on the surface of antigen-presenting cells, including B-cells, and provides co-stimulation to regulatory T-cells (Treg) through CD2 receptor binding. Tregs appear to be essential suppressors of tissue-specific autoimmune responses. Thereby, CD58 plays protective role in multiple sclerosis (MS) and CD58 was identified among several loci associated with MS susceptibility. Minor (C) variant of the single-nucleotide polymorphism (SNP) rs1335532 is associated with lower MS risk according to genome-wide association studies (GWAS) and its presence correlates with higher CD58 mRNA levels in MS patients...
July 10, 2018: Biochimica et Biophysica Acta
Indu Ambudkar
Salivary glands secrete saliva, a mixture of proteins and fluids, which plays an extremely important role in the maintenance of oral health. Loss of salivary secretion causes a dry mouth condition, xerostomia, which has numerous deleterious consequences including opportunistic infections within the oral cavity, difficulties in eating and swallowing food, and problems with speech. Saliva secretion is regulated by stimulation of specific signaling mechanisms within the acinar cells of the gland. Neurotransmitter-stimulated increase in cytosolic [Ca2+ ] ([Ca2+ ]i ) in acinar cells is the primary trigger for salivary fluid secretion from salivary glands, the loss of which is a critical factor underlying dry mouth conditions in patients...
July 10, 2018: Biochimica et Biophysica Acta
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