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Timothy J Bergmann, Ilaria Fregno, Fiorenza Fumagalli, Andrea Rinaldi, Francesco Bertoni, Paul J Boersema, Paola Picotti, Maurizio Molinari
The stress sensors ATF6, IRE1 and PERK monitor deviations from homeostatic conditions in the endoplasmic reticulum (ER), a protein biogenesis compartment of eukaryotic cells. Their activation elicits unfolded protein responses (UPR) to re-establish proteostasis. UPR have been extensively investigated in cells exposed to chemicals that activate ER stress sensors by perturbing calcium, N-glycans or redox homeostasis. Cell responses to variations in luminal load with unfolded proteins are, in contrast, poorly characterized...
February 16, 2018: Journal of Biological Chemistry
Carrie R Sowers, Rong Wang, Rebecca A Bourne, Barbara C McGrath, Jingjie Hu, Sarah C Bevilacqua, James C Paton, Adrienne W Paton, Sophie Collardeau-Frachon, Marc Nicolino, Douglas R Cavener
Loss-of-function mutations of the protein kinase PERK (EIF2AK3) in humans and mice cause permanent neonatal diabetes and severe proinsulin aggregation in the endoplasmic reticulum (ER), highlighting the essential role of PERK in insulin production in pancreatic β cells. As PERK is generally known as a translational regulator of the Unfolded Protein Response (UPR), the underlying cause of these β cell defects has often been attributed to derepression of proinsulin synthesis, resulting in proinsulin overload in the ER...
February 14, 2018: Journal of Biological Chemistry
Wei Wei, Saurav Misra, Matthew V Cannon, Renchi Yang, Xiaofan Zhu, Reid Gilmore, Min Zhu, Bin Zhang
N-glycosylation is a common posttranslational modification of secreted and membrane proteins, catalyzed by the two enzymatic isoforms of the oligosaccharyltransferase, STT3A and STT3B. Missense mutations are the most common mutations in inherited diseases, however, missense mutations that generate extra, non-native N-glycosylation sites have not been well characterized. Coagulation factor VIII (FVIII) contains five consensus N-glycosylation sites outside its functionally dispensable B domain. We developed a computer program that identified hemophilia A mutations in FVIII that can potentially create ectopic glycosylation sites...
February 14, 2018: Biochemical Journal
Subramanyam Dasari, Angela Lincy Prem Antony Samy, Andre Kajdacsy-Balla, Maarten C Bosland, Gnanasekar Munirathinam
The aim of this study was to evaluate the therapeutic effects of vitamin K2 (VK2) on castration-resistant prostate cancer (CRPC) and its anti-cancer mechanisms in a pre-clinical study using a VCaP cell line (ATCC ® CRL-2876™) which was established from a vertebral bone metastasis from a patient with hormone refractory prostate cancer. Our data showed that VK2 significantly inhibited CRPC VCaP cell proliferation in a dosedependent manner at 48 h treatment in vitro. In addition, VK2 reduced the migration potential of VCaP cells and inhibited anchorage-independent growth of these cells...
February 9, 2018: Food and Chemical Toxicology
Miri Lutski, Salo Haratz, Galit Weinstein, Uri Goldbourt, David Tanne
Background: Recent studies suggest that impaired cerebrovascular reactivity (CVR), a marker of cerebral microvascular damage, is associated with a higher risk of stroke, cognitive decline and mortality. We tested whether abnormal cerebrovascular status is associated with late-life frailty among men with pre-existing cardiovascular disease. Methods: A subset of 327 men (mean age at baseline 56.7±6.5 years) who previously participated in the Bezafibrate Infarction Prevention (BIP) trial (1990-1997) and then in the BIP Neurocognitive study underwent a neurovascular evaluation 14...
February 8, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
J Hu, Z C Chen, Y Z Zhang, P Han, W J Ma, Q Zhang, M Xu
Objective: To test the mechanism and upstream pathway of outer hair cell apoptosis in Cadherin 23 (Cdh23) gene mutant mice. Method: The mutant Cdh23(erl/erl)(erl) mice were collected as the study group, while the C57BL/6J (B6) mice were chosen as the control group. A total of 70 mice per group were used in this study. The study group and control group underwent auditory-evoked brainstem response (ABR) tests at the same age. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to detect outer hair cell(OHC) apoptosis...
February 7, 2018: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
Salomon M Stemmer, Ofer Benjaminov, Michael H Silverman, Uziel Sandler, Ofer Purim, Naomi Sender, Chen Meir, Pnina Oren-Apoteker, Joel Ohana, Yoram Devary
The aim of the present phase I first-in-human study was to investigate the safety/efficacy of dTCApFs (a novel hormone peptide that enters cells through the T1/ST2 receptor), in advanced/metastatic solid tumors. The primary objective of this open-label dose-escalation study was to determine the safety profile of dTCApFs. The study enrolled patients (aged ≥18 years) with pathologically confirmed locally advanced/metastatic solid malignancies, who experienced treatment failure or were unable to tolerate previous standard therapy...
January 2018: Molecular and Clinical Oncology
M C Zarcone, E Duistermaat, M J Alblas, A van Schadewijk, D K Ninaber, V Clarijs, M M Moerman, D Vaessen, P S Hiemstra, I M Kooter
Harmful effects of diesel emissions can be investigated via exposures of human epithelial cells, but most of previous studies have largely focused on the use of diesel particles or emission sources that are poorly representative of engines used in current traffic. We studied the cellular response of primary bronchial epithelial cells (PBECs) at the air-liquid interface (ALI) to the exposure to whole diesel exhaust (DE) generated by a Euro V bus engine, followed by treatment with UV-inactivated non-typeable Haemophilus influenzae (NTHi) bacteria to mimic microbial exposure...
February 8, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
L A Avila, R Chandrasekar, K E Wilkinson, J Balthazor, M Heerman, J Bechard, S Brown, Y Park, S Dhar, G R Reeck, J M Tomich
Development of new and specific insect pest management methods is critical for overcoming pesticide resistance and collateral off-target killings. Gene silencing by feeding dsRNA to insects shows promise in this area. Here we described the use of a peptide nano-material, branched amphiphilic peptide capsules (BAPCs), that facilitates cellular uptake of dsRNA by insects through feeding. The insect diets included dsRNA with and without complexation with BAPCs. The selected insect species come from two different orders with different feeding mechanisms: Tribolium castaneum and Acyrthosiphon pisum...
January 31, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Hideaki Yano, Alessandro Bonifazi, Min Xu, Daryl A Guthrie, Stephanie N Schneck, Ara M Abramyan, Andrew D Fant, W Conrad Hong, Amy H Newman, Lei Shi
The sigma 1 receptor (σ1R) is a structurally unique transmembrane protein that functions as a molecular chaperone in the endoplasmic reticulum (ER), and has been implicated in cancer, neuropathic pain, and psychostimulant abuse. Despite physiological and pharmacological significance, mechanistic underpinnings of structure-function relationships of σ1R are poorly understood, and molecular interactions of selective ligands with σ1R have not been elucidated. The recent crystallographic determination of σ1R as a homo-trimer provides the foundation for mechanistic elucidation at the molecular level...
January 30, 2018: Neuropharmacology
Hsiao-Chen Tu, Yung-Chun Hsiao, Wan-Yu Yang, Shin-Lin Tsai, Hua-Kuo Lin, Chong-Yi Liao, Jeng-Wei Lu, Yu-Ting Chou, Horng-Dar Wang, Chiou-Hwa Yuh
α-1,2 mannosidases, key enzymes in N-glycosylation, are required for the formation of mature glycoproteins in eukaryotes. Aberrant regulation of α-1,2 mannosidases can result in cancer, although the underlying mechanisms are unclear. Here, we report the distinct roles of α-1,2 mannosidase subtypes (MAN1A, MAN1B, ERMAN1, MAN1C) in the formation of hepatocellular carcinoma (HCC). Clinicopathological analyses revealed that the clinical stage, tumor size, α-fetoprotein level, and invasion status were positively correlated with the expression levels of MAN1A1, MAN1B1, and MAN1A2...
May 2017: Hepatology Communications
Akiko Sekiguchi, Sei-Ichiro Motegi, Akihiko Uchiyama, Akihito Uehara, Chisako Fujiwara, Sahori Yamazaki, Buddhini Perera, Hideharu Nakamura, Sachiko Ogino, Yoko Yokoyama, Ryoko Akai, Takao Iwawaki, Osamu Ishikawa
BACKGROUND: We previously identified that botulinum toxin A (BTX-A) suppressed pressure ulcer (PU) formation after cutaneous ischemia-reperfusion (I/R) injury; however, regulation of cutaneous I/R-induced oxidative and endoplasmic reticulum (ER) stress by BTX-B was not investigated. Additionally, the efficacy of BTX-B injection has never been examined. OBJECTIVE: Objective was to assess the effects of BTX-B on the formation of PU by cutaneous I/R injury, and the regulation of oxidative and ER stress in I/R injury by BTX-B...
February 2, 2018: Journal of Dermatological Science
Qiuyu Wang, Peng Wang, Zhigang Xiao
Resistant starch is as common soluble fiber that escapes digestion in the small intestine and can regulate intestinal function, metabolism of blood glucose and lipids, and may prevent tumorigenesis of gastrointestinal cancer. Epidemiology and other evidence have suggested that resistant starch may prevent colon cancer development. The aim of the current study was to explore the ameliorative effects and potential mechanisms of resistant starch in the tumorigenesis of colon tumors induced by dimethylhydrazine in C57BL/6 mice...
January 25, 2018: International Journal of Molecular Medicine
Chopperla Ramakrishna, Sonam Singh, Sangala Raghavendrarao, Jasdeep C Padaria, Sasmita Mohanty, Tilak Raj Sharma, Amolkumar U Solanke
The occurrence of various stresses, as the outcome of global climate change, results in the yield losses of crop plants. Prospecting of genes in stress tolerant plant species may help to protect and improve their agronomic performance. Finger millet (Eleusine coracana L.) is a valuable source of superior genes and alleles for stress tolerance. In this study, we isolated a novel endoplasmic reticulum (ER) membrane tethered bZIP transcription factor from finger millet, EcbZIP17. Transgenic tobacco plants overexpressing this gene showed better vegetative growth and seed yield compared with wild type (WT) plants under optimal growth conditions and confirmed upregulation of brassinosteroid signalling genes...
February 1, 2018: Scientific Reports
Njogu M Kimani, Josphat C Matasyoh, Marcel Kaiser, Reto Brun, Thomas J Schmidt
In the endeavor to obtain new antitrypanosomal agents, particularly sesquiterpene lactones, from Kenyan plants of the family Asteraceae, Vernonia cinerascens Sch. Bip. was investigated. Bioactivity-guided fractionation and isolation in conjunction with LC/MS-based dereplication has led to the identification of vernodalol (1) and isolation of vernodalin (2), 11β,13-dihydrovernodalin (3), 11β,13-dihydrovernolide (4), vernolide (5), 11β,13-dihydrohydroxyvernolide (6), hydroxyvernolide (7), and a new germacrolide type sesquiterpene lactone vernocinerascolide (8) from the dichloromethane extract of V...
January 27, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Nozomu Okino, Hiroyoshi Wakisaka, Yohei Ishibashi, Makoto Ito
Thraustochytrids are single cell marine eukaryotes that produce large amounts of polyunsaturated fatty acids such as docosahexaenoic acid. In the present study, we report the visualization of endoplasmic reticulum (ER) and mitochondria in a type strain of the thraustochytrid, Aurantiochytrium limacinum ATCC MYA-1381, using the enhanced green fluorescent protein (EGFP) with specific targeting/retaining signals. We expressed the egfp gene with ER targeting/retaining signals from A. limacinum calreticulin or BiP/GRP78 in the thraustochytrid, resulting in the distribution of EGFP signals at the perinuclear region and near lipid droplets...
January 29, 2018: Marine Biotechnology
Qilin Li, Md Asif Ahsan, Hongjun Chen, Jitong Xue, Ming Chen
Most of non-coding RNAs are considered to express at low levels and have a limited phylogenetic distribution in the cytoplasm, meaning that they may be only involved in specific biological processes. However, recent studies showed the protein-coding potential of ncRNAs, indicating that they might be source of some special proteins. Although there are increasing non-coding RNAs identified to be able to code proteins, it is challenging to distinguish coding RNAs from previously annotated ncRNAs, and to detect the proteins from their translation...
January 27, 2018: ACS Synthetic Biology
S Damodaraiah, V Reddy Prasad, Y C Ratnakaram
In the present study, the effect of bismuth oxide (Bi2 O3 ) content on the structural and optical properties of 0.5Sm3+ -doped phosphate glass and the effect of concentration on structural and optical properties of Sm3+ -doped bismuth phosphate (BiP) glass were studied. Structural characterization was accomplished using X-ray diffraction (XRD), scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS), Fourier transform infrared (FTIR) spectroscopy and 31 P nuclear magnetic resonance (NMR) spectroscopy...
January 24, 2018: Luminescence: the Journal of Biological and Chemical Luminescence
Naima Chalour, Agathe Maoui, Patrice Rat, France Massicot, Melody Dutot, Anne-Marie Faussat, Estelle Devevre, Astrid Limb, Jean-Michel Warnet, Jacques Treton, Virginie Dinet, Frederic Mascarelli
BACKGROUND: Alzheimer's disease (AD) and age-related macular degeneration (AMD) present similarities, particularly with respect to oxidative stress, including production of 4-Hydroxy-2-nonenal (HNE). AMD has been named the AD in the eye. The Müller cells (MC) function as a principal glia of the retina and maintain water/potassium, glutamate homeostasis and redox status. Any MC dysfunction results in retinal neurodegeneration. OBJECTIVES: We investigated the effects of HNE in human MC...
January 18, 2018: Current Alzheimer Research
Hyo-Jin Park, Jae-Young Park, Jin-Woo Kim, Seul-Gi Yang, Jae-Min Jung, Min-Ji Kim, Joung Jun Park, Deog-Bon Koo
In the present study, we investigated the role of binding immunoglobulin protein/glucose-regulated protein, 78-kDa (BIP/GRP78)-regulated endoplasmic reticulum (ER)-stress on meiotic maturation and cumulus cells expansion in porcine cumulus-oocyte complexes (COCs). Previously, it has been demonstrated that unfolded protein response (UPR)-related genes, such as molecules involved in ER-stress defense mechanisms, were expressed in matured oocytes and cumulus cells during in vitro maturation (IVM) of porcine oocytes...
December 2017: Balsaeng'gwa Saengsig
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