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Liu Xianchu, Liu Ming, Liu Xiangbin, Zheng Lan
Background: Grape seed proanthocyanidin extract (GSPE) has been extensively reported to possess a wide range of beneficial properties in multiple tissue damage. Previous studies have shown that exhaustive exercise-induced fatigue associates with oxidative stress injury, inflammatory response, and mitochondrial dysfunction. Objective: The aim of this study is to investigate the anti-fatigue effects of GSPE in mice and explore its possible underlying mechanism. Design: The mouse model of exhaustive exercise-induced fatigue was established by using the forced swimming test, and GSPE was orally treated for successive 28 days at 0, 1, 50 and 100 mg/kg/day of body weight, designated the control, GSPE-L, GSPE-M and GSPE-H groups, respectively...
2018: Food & Nutrition Research
Doaa M Mokhtar
Fish liver is considered as a key organ that controls various life functions. The cellular and stromal elements of liver of eighteen specimens of adult grass carp were investigated by light- and electron- microscopy and enzyme histochemistry. The liver was formed of two lobes with a long process extended from the right lobe. Serial paraffin section of the liver identified different kinds of vascular- biliary structures as follows: 1) pancreatic-venous-biliary-arteriolar tracts (P-VBAT); 2) venous-biliary-arteriolar tracts, (VBAT); 3) pancreatic-venous-biliary tracts (P-VBT); 4) venous-biliary tracts (VBT); 5) venous-arteriolar tracts (VAT); 6) isolated veins named as venous tracts (VT); 7) isolated bile ducts, named as biliary tracts (BT); 8) biliary-arteriolar tracts (BAT); 9) pancreatic-biliary tracts (P-BT); 10) pancreatic- venous tracts (P-VT)...
June 6, 2018: Micron: the International Research and Review Journal for Microscopy
Valerie Matagne, Joyce Wondolowski, Matthew Frerking, Mohammad Shahidullah, Nicholas A Delamere, Ursula S Sandau, Sarojini Budden, Sergio R Ojeda
Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the MECP2 gene. In the absence of MeCP2/MECP2, expression of FXYD domain-containing transport regulator 1 (FXYD1) is deregulated in the frontal cortex (FC) of mice and humans. Because FXYD1 is a membrane protein that controls cell excitability by modulating Na+ , K+ -ATPase activity (NKA), an excess of FXYD1 may reduce NKA activity and contribute to the neuronal phenotype of Mecp2 deficient (KO) mice. To determine if FXYD1 can rescue these RTT deficits, we studied the male progeny of Fxyd1 null males bred to heterozygous Mecp2 female mice...
June 11, 2018: Brain Research
Li Zhang, Xian Cheng, Shichen Xu, Jiandong Bao, Huixin Yu
BACKGROUND: Thyroid cancer is the most common endocrine tumor. Our previous studies have demonstrated that curcumin can induce apoptosis in human papillary thyroid carcinoma BCPAP cells. However, the underlined mechanism has not been clearly elucidated. Endoplasmic reticulum (ER) is a major organelle for synthesis, maturation, and folding proteins as well as a large store for Ca. Overcoming chronically activated ER stress by triggering pro-apoptotic pathways of the unfolded protein response (UPR) is a novel strategy for cancer therapeutics...
June 2018: Medicine (Baltimore)
V B Berdichevskii, B A Berdichevskii
The search for and use of alternative biomarkers of the hyperactive bladder has garnered increasing attention in recent years because they may be considered pathogenetically significant and used as surrogate biomarkers. Promising agents that have met these criteria include proteins cytokines, neurotrophins, tumor necrosis factor (TNF), nerve growth factor (NGF), fibrinopeptides A and B, C-reactive protein, membrane-bound ATPase. Analysis of current scientific literature has demonstrated that specialists in many fields of medicine show interest in endogenous proteins that do not belong to neurotransmitters but affect the contractile ability of myocytes...
May 2018: Urologii︠a︡
Changhwan Ahn, Jong-Sam Choi, Eui-Bae Jeung
Transmembrane cation channels include those for calcium, copper and iron ion transport. Each channel has physiological significance, and all have been associated with disease. However, the comparative study of transcriptional‑translational levels in canine organs has not been previously reported. In the present study, organ‑specific expression of calcium channels, including sodium/potassium/calcium exchanger 3 (NCKX3) and transient receptor potential cation channel subfamily V member 2 (TRPV2), copper channels, including high affinity copper uptake protein 1 (CTR1) and copper‑transporting ATPase 1 (ATP7A), and iron channels, including iron‑regulated transporter 1 (IREG1) and hephaestin (HEPH) proteins and their mRNAs were examined in the canine duodenum, kidney, spleen and liver...
June 7, 2018: Molecular Medicine Reports
Le Gui, Xin Guo, Zhe Zhang, Hui Xu, Ya-Wei Ji, Ren-Jun Wang, Jiang-Hua Zhu, Qing-Hui Chen
Activation of the Ca2+ /calmodulin-dependent protein kinase II isoform δA (CaMKIIδA) disturbs intracellular Ca2+ homeostasis in cardiomyocytes during chronic heart failure (CHF). We hypothesized that upregulation of CaMKIIδA in cardiomyocytes might enhance Ca2+ leak from the sarcoplasmic reticulum (SR) via activation of phosphorylated ryanodine receptor type 2 (P-RyR2) and decrease Ca2+ uptake by inhibition of SR calcium ATPase 2a (SERCA2a). In this study, CHF was induced in rats by ligation of the left anterior descending coronary artery...
June 14, 2018: Acta Pharmacologica Sinica
Olga Kuchuk, Alessandra Tuccitto, Davide Citterio, Veronica Huber, Chiara Camisaschi, Massimo Milione, Barbara Vergani, Antonello Villa, Malcolm Ronald Alison, Simone Carradori, Claudiu T Supuran, Licia Rivoltini, Chiara Castelli, Vincenzo Mazzaferro
Interfering with tumor metabolism is an emerging strategy for treating cancers that are resistant to standard therapies. Featuring a rapid proliferation rate and exacerbated glycolysis, hepatocellular carcinoma (HCC) creates a highly hypoxic microenvironment with excessive production of lactic and carbonic acids. These metabolic conditions promote disease aggressiveness and cancer-related immunosuppression. The pH regulatory molecules work as a bridge between tumor cells and their surrounding milieu. Herein, we show that the pH regulatory molecules CAIX, CAXII and V-ATPase are overexpressed in the HCC microenvironment and that interfering with their pathways exerts antitumor activity...
2018: Oncoimmunology
Run-Ze Li, Xing-Xing Fan, Fu-Gang Duan, Ze-Bo Jiang, Hu-Dan Pan, Lian-Xiang Luo, Yan-Ling Zhou, Ying Li, Ying-Jia Yao, Xiao-Jun Yao, Elaine Lai-Han Leung, Liang Liu
Non-small-cell lung cancer (NSCLC) is the predominant histological type of lung cancer and is characterized by the highest mortality and incidence rates among these types of malignancies. Cardiac glycosides, a class of natural products, have been identified as a potential type of chemotherapeutic agent. This study aims to investigate the anti-cancer effects and the mechanisms of action of Proscillaridin A (P.A) in NSCLC cells. In vitro sodium-potassium pump (Na+ /K+ ATPase) enzyme assays indicated that P.A is a direct Na+ /K+ ATPase inhibitor...
June 13, 2018: Cell Death & Disease
Daniel H Lin, Ana R Correia, Sarah W Cai, Ferdinand M Huber, Claudia A Jette, André Hoelz
The nuclear pore complex (NPC) controls the passage of macromolecules between the nucleus and cytoplasm, but how the NPC directly participates in macromolecular transport remains poorly understood. In the final step of mRNA export, the DEAD-box helicase DDX19 is activated by the nucleoporins Gle1, Nup214, and Nup42 to remove Nxf1•Nxt1 from mRNAs. Here, we report crystal structures of Gle1•Nup42 from three organisms that reveal an evolutionarily conserved binding mode. Biochemical reconstitution of the DDX19 ATPase cycle establishes that human DDX19 activation does not require IP6 , unlike its fungal homologs, and that Gle1 stability affects DDX19 activation...
June 13, 2018: Nature Communications
Ya-Ju Sung, Ting-Yu Kao, Cheng-Liang Kuo, Chi-Chen Fan, An Ning Cheng, Wei-Cheng Fang, Han-Yu Chou, Yu-Kang Lo, Chung-Hsing Chen, Shih Sheng Jiang, I-Shou Chang, Chun-Hua Hsu, Jin-Ching Lee, Alan Yueh-Luen Lee
Mitochondrial Lon is a multi-function matrix protease with chaperone activity. However, little literature has been undertaken into detailed investigations on how Lon regulates apoptosis through its chaperone activity. Accumulating evidences indicate that various stresses induce transportation of p53 to mitochondria and activate apoptosis in a transcription-independent manner. Here we found that increased Lon interacts with p53 in mitochondrial matrix and restrains the apoptosis induced by p53 under oxidative stress by rescuing the loss of mitochondrial membrane potential (Δψm) and the release of cytochrome C and SMAC/Diablo...
June 13, 2018: Cell Death & Disease
Franziska Bleichert, Alexander Leitner, Ruedi Aebersold, Michael R Botchan, James M Berger
In eukaryotes, the heterohexameric origin recognition complex (ORC) coordinates replication onset by facilitating the recruitment and loading of the minichromosome maintenance 2-7 (Mcm2-7) replicative helicase onto DNA to license origins. Drosophila ORC can adopt an autoinhibited configuration that is predicted to prevent Mcm2-7 loading; how the complex is activated and whether other ORC homologs can assume this state are not known. Using chemical cross-linking and mass spectrometry, biochemical assays, and electron microscopy (EM), we show that the autoinhibited state of Drosophila ORC is populated in solution, and that human ORC can also adopt this form...
June 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
Riki Terui, Koji Nagao, Yoshitaka Kawasoe, Kanae Taki, Torahiko L Higashi, Seiji Tanaka, Takuro Nakagawa, Chikashi Obuse, Hisao Masukata, Tatsuro S Takahashi
Post-replicative correction of replication errors by the mismatch repair (MMR) system is critical for suppression of mutations. Although the MMR system may need to handle nucleosomes at the site of chromatin replication, how MMR occurs in the chromatin environment remains unclear. Here, we show that nucleosomes are excluded from a >1-kb region surrounding a mismatched base pair in Xenopus egg extracts. The exclusion was dependent on the Msh2-Msh6 mismatch recognition complex but not the Mlh1-containing MutL homologs and counteracts both the HIRA- and CAF-1 (chromatin assembly factor 1)-mediated chromatin assembly pathways...
June 13, 2018: Genes & Development
Richard W Hill, Eric J Armstrong, Kazuo Inaba, Masaya Morita, Martin Tresguerres, Jonathon H Stillman, Jinae N Roa, Garfield T Kwan
The giant clam Tridacna crocea , native to Indo-Pacific coral reefs, is noted for its unique ability to bore fully into coral rock and is a major agent of reef bioerosion. However, T. crocea 's mechanism of boring has remained a mystery despite decades of research. By exploiting a new, two-dimensional pH-sensing technology and manipulating clams to press their presumptive boring tissue (the pedal mantle) against pH-sensing foils, we show that this tissue lowers the pH of surfaces it contacts by greater than or equal to 2 pH units below seawater pH day and night...
June 2018: Biology Letters
Susana Peralta, Steffi Goffart, Sion L Williams, Francisca Diaz, Sofia Garcia, Nadee Nissanka, Estela Area-Gomez, Jaakko Pohjoismäki, Carlos T Moraes
Mutations in the mitochondrial inner membrane ATPase ATAD3A result in neurological syndromes in humans. In mice, the ubiquitous disruption of Atad3 was embryonic lethal, but a skeletal muscle specific conditional knockout (cKO) was viable. At birth, ATAD3 muscle cKO mice had normal weight, but from 2 months onwards showed progressive motor-impaired coordination and weakness. Loss of ATAD3 caused early and severe mitochondrial structural abnormalities, mitochondrial proliferation and muscle atrophy. There was dramatic reduction in mitochondrial cristae junctions and overall cristae morphology...
June 13, 2018: Journal of Cell Science
Hong Ren, Mee Yeon Park, Angela K Spartz, Jeh Haur Wong, William M Gray
The plant hormone auxin regulates numerous growth and developmental processes throughout the plant life cycle. One major function of auxin in plant growth and development is the regulation of cell expansion. Our previous studies have shown that SMALL AUXIN UP RNA (SAUR) proteins promote auxin-induced cell expansion via an acid growth mechanism. These proteins inhibit the PP2C.D family phosphatases to activate plasma membrane (PM) H+-ATPases and thereby promote cell expansion. However, the functions of individual PP2C...
June 13, 2018: PLoS Genetics
Daniel B Yaeger, Emma J Coddington
Neurons in the medullary reticular formation are involved in the control of postural and locomotor behaviors in all vertebrates. Reticulospinal neurons in this brain region provide one of the major descending projections to the spinal cord. Although neurons in the newt medullary reticular formation have been extensively studied using in vivo extracellular recordings, little is known of their intrinsic biophysical properties or of the underlying circuitry of this region. Using whole-cell patch-clamp recordings in brain slices containing the rostromedial reticular formation (rmRF) from adult male newts, we observed spontaneous miniature outward currents (SMOCs) in approximately two-thirds of neurons...
June 13, 2018: Journal of Neurophysiology
Cristina Uribe-Alvarez, Natalia Chiquete-Félix, Lilia Morales-García, Arlette Bohórquez-Hernández, Norma Laura Delgado-Buenrostro, Luis Vaca, Antonio Peña, Salvador Uribe-Carvajal
Wolbachia sp. has colonized over 70% of insect species, successfully manipulating host fertility, protein expression, lifespan, and metabolism. Understanding and engineering the biochemistry and physiology of Wolbachia holds great promise for insect vector-borne disease eradication. Wolbachia is cultured in cell lines, which have long duplication times and are difficult to manipulate and study. The yeast strain Saccharomyces cerevisiae W303 was used successfully as an artificial host for Wolbachia wAlbB. As compared to controls, infected yeast lost viability early, probably as a result of an abnormally high mitochondrial oxidative phosphorylation activity observed at late stages of growth...
June 13, 2018: MicrobiologyOpen
X-R Chang, Y-L Yao, D Wang, H-T Ma, P-H Gou, C-Y Li, J-L Wang
Thyroid hormone deficiency can impair testicular function. However, knowledge of the effects of mitogen-activated protein kinase (MAPK) pathways on testicular mitochondrial oxidative damage induced by hypothyroidism is still rudimentary. This study aims to explore the possible mechanisms of testicular mitochondrial oxidative damage in hypothyroidism rats. Wistar male rats were randomly divided into control (C), low- (L), and high-hypothyroidism (H) groups (1 ml/100 g body weights (BWs)/day 0, 0.001% and 0.1% propylthiouracil, respectively) by intragastric gavage for 60 days...
January 1, 2018: Human & Experimental Toxicology
Bruno G Aguiar, Prasad K Padmanabhan, Carole Dumas, Barbara Papadopoulou
VCP/p97/Cdc48 is one of the best-characterized type II cytosolic AAA+ ATPases most known for their role in ubiquitin-dependent protein quality control. Here, we provide functional insights into the role of the Leishmania VCP/p97 homolog (LiVCP) in the parasite intracellular development. We demonstrate that although LiVCP is an essential gene, L. infantum promastigotes can grow with less VCP. In contrast, growth of axenic and intracellular amastigotes is dramatically affected upon decreased LiVCP levels in heterozygous and temperature sensitive LiVCP mutants or the expression of dominant negative mutants known to specifically target the second conserved VCP ATPase domain, a major contributor of the VCP overall ATPase activity...
June 12, 2018: Cellular Microbiology
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