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Akhi Akhter, Emanuel Rosonina
The Saccharomyces cerevisiae transcription factor Gcn4 is expressed during amino acid starvation and its abundance is controlled by ubiquitin-mediated proteolysis. Cdk8, a kinase component of the RNA polymerase II Mediator complex, phosphorylates Gcn4 which triggers its ubiquitination/proteolysis and is thought to link Gcn4 degradation with transcription of target genes. In addition to phosphorylation and ubiquitination, we previously showed that Gcn4 becomes sumoylated in a DNA-binding dependent manner, while a non-sumoylatable form of Gcn4 showed increased chromatin occupancy, but only if Cdk8 was present...
October 21, 2016: Genetics
Oznur Bayraktar, Ozlem Oral, Nur Mehpare Kocaturk, Yunus Akkoc, Karin Eberhart, Ali Kosar, Devrim Gozuacik
The ubiquitin-proteasome system (UPS) degrades soluble proteins and small aggregates, whereas macroautophagy (autophagy herein) eliminates larger protein aggregates, tangles and even whole organelles in a lysosome-dependent manner. VCP/p97 was implicated in both pathways. VCP/p97 mutations cause a rare multisystem disease called IBMPFD (Inclusion Body Myopathy with Paget's Disease and Frontotemporal Dementia). Here, we studied the role IBMPFD-related mutants of VCP/p97 in autophagy. In contrast with the wild-type VCP/p97 protein or R155C or R191Q mutants, the P137L mutant was aggregate-prone...
2016: PloS One
Daniel Jaeger, Christian Pilger, Henning Hachmeister, Elina Oberländer, Robin Wördenweber, Julian Wichmann, Jan H Mussgnug, Thomas Huser, Olaf Kruse
Oleaginous photosynthetic microalgae hold great promise as non-food feedstocks for the sustainable production of bio-commodities. The algal lipid quality can be analysed by Raman micro-spectroscopy, and the lipid content can be imaged in vivo in a label-free and non-destructive manner by coherent anti-Stokes Raman scattering (CARS) microscopy. In this study, both techniques were applied to the oleaginous microalga Monoraphidium neglectum, a biotechnologically promising microalga resistant to commonly applied lipid staining techniques...
October 21, 2016: Scientific Reports
Yan Long, Wen-Bin Tsai, Jeffrey T Chang, Marcos Estecio, Medhi Wangpaichitr, Naramol Savaraj, Lynn G Feun, Helen H W Chen, Macus Tien Kuo
Many human tumors require extracellular arginine (Arg) for growth because the key enzyme for de novo biosynthesis of Arg, argininosuccinate synthetase 1 (ASS1), is silenced. These tumors are sensitive to Arg-starvation therapy using pegylated arginine deiminase (ADI-PEG20) which digests extracellular Arg. Many previous studies reported that ASS1 silencing is due to epigenetic inactivation of ASS1 expression by DNA methylation, and that the demethylation agent 5-aza-deoxycytidine (Aza-dC) can induce ASS1 expression...
September 28, 2016: Oncotarget
Antonella Conforti, Nadia Starc, Simone Biagini, Luigi Tomao, Angela Pitisci, Mattia Algeri, Pietro Sirleto, Antonio Novelli, Giulia Grisendi, Olivia Candini, Cintia Carella, Massimo Dominici, Franco Locatelli, Maria Ester Bernardo
The risk of malignant transformation of ex-vivo expanded human mesenchymal stromal cells (huMSCs) has been debated in the last years; however, the biosafety of these cells after exposure to supramaximal physical and chemical stress has never been systematically investigated.We established an experimental in vitro model to induce supramaximal physical (ionizing radiation, IR) and chemical (starvation) stress on ex-vivo expanded bone marrow (BM)-derived huMSCs and investigated their propensity to undergo malignant transformation...
October 15, 2016: Oncotarget
Shu Yang, Anne Rosenwald
Macroautophagy, a highly conserved process in eukaryotic cells, is initiated in response to stress, especially nutrient starvation. Macroautophagy helps cells survive by engulfing proteins and organelles into an unusual double-membraned structure called the autophagosome, which then fuses with the lysosome. Upon degradation of the engulfed contents, the building blocks are recycled for synthesis of new macromolecules. Recent work has demonstrated that construction of the autophagosome requires a variety of small GTPases in variations of their normal roles in membrane traffic...
October 20, 2016: Small GTPases
Chengchen Li, Caifeng Li, Haiyan Zhang, Hong Liao, Xiurong Wang
Induction of secreted and intracellular purple acid phosphatases (PAPs; EC is widely recognized as an adaptation of plants to phosphorus (P) deficiency. The secretion of PAPs plays important roles in P acquisition. However, little is known about the functions of intracellular PAP in plants and nodules. In this work, we identified a novel PAP gene GmPAP21 in soybean. Expression of GmPAP21 was induced by P limitation in nodules, roots and old leaves, and increased in roots with increasing duration of P starvation...
October 20, 2016: Physiologia Plantarum
Marissa B Guzzo, Hoa T Nguyen, Thanh H Pham, Monika Wyszczelska-Rokiel, Hieronim Jakubowski, Kerstin A Wolff, Sam Ogwang, Joseph L Timpona, Soumya Gogula, Michael R Jacobs, Markus Ruetz, Bernhard Kräutler, Donald W Jacobsen, Guo-Fang Zhang, Liem Nguyen
The methylfolate trap, a metabolic blockage associated with anemia, neural tube defects, Alzheimer's dementia, cardiovascular diseases, and cancer, was discovered in the 1960s, linking the metabolism of folate, vitamin B12, methionine and homocysteine. However, the existence or physiological significance of this phenomenon has been unknown in bacteria, which synthesize folate de novo. Here we identify the methylfolate trap as a novel determinant of the bacterial intrinsic death by sulfonamides, antibiotics that block de novo folate synthesis...
October 2016: PLoS Pathogens
Yong Li, Julia Hoffmann, Yang Li, Flora Stephano, Iris Bruchhaus, Christine Fink, Thomas Roeder
The monoamines octopamine (OA) and tyramine (TA) modulate numerous behaviours and physiological processes in invertebrates. Nevertheless, it is not clear whether these invertebrate counterparts of norepinephrine are important regulators of metabolic and life history traits. We show that flies (Drosophila melanogaster) lacking OA are more resistant to starvation, while their overall life span is substantially reduced compared with control flies. In addition, these animals have increased body fat deposits, reduced physical activity and a reduced metabolic resting rate...
October 19, 2016: Scientific Reports
Stefano Papazian, Eliezer Khaling, Christelle Bonnet, Steve Lassueur, Philippe Reymond, Thomas Moritz, James Blande, Benedicte Riber Albrectsen
Plants have evolved adaptive mechanisms that allow them to tolerate a continuous range of abiotic and biotic stressors. Tropospheric ozone (O3), a global anthropogenic pollutant, directly affects living organisms and ecosystems, including plant-herbivore interactions. In this study, we investigate the stress responses of wild black mustard (Brassica nigra) exposed consecutively to O3 and the specialist herbivore Pieris brassicae. Transcriptomics and metabolomics data were evaluated using multivariate, correlation, and network analyses for the O3 and herbivory responses...
October 6, 2016: Plant Physiology
Mariana Pavel, David C Rubinsztein
Autophagy (literally "self-eating") is an evolutionarily conserved degradation process where cytoplasmic components are engulfed by vesicles called autophagosomes, which are then delivered to lysosomes, where their contents are degraded. Under stress conditions, such as starvation or oxidative stress, autophagy is upregulated in order to degrade macromolecules and restore the nutrient balance. The source of membranes that participate in the initial formation of phagophores is still incompletely understood and many intracellular structures have been shown to act as lipid donors, including the endoplasmic reticulum, Golgi, nucleus, mitochondria and the plasma membrane...
October 18, 2016: FEBS Journal
Cong Tang, Stefan Offermanns
The short-chain fatty acid receptors FFA2 (GPR43) and FFA3 (GPR41) are activated by acetate, propionate, and butyrate. These ligands are produced by bacteria in the gut. In addition, the body itself can in particular produce acetate, and acetate plasma levels have been shown to be increased, e.g., in diabetic patients or during periods of starvation. FFA2 and FFA3 are both expressed by enteroendocrine cells and pancreatic β-cells. In addition, FFA2 is found on immune cells and adipocytes, whereas FFA3 is expressed by some peripheral neurons...
October 19, 2016: Handbook of Experimental Pharmacology
Nataly E Gruntenko, Natalya V Adonyeva, Elena V Burdina, Evgenia K Karpova, Olga V Andreenkova, Daniil V Gladkikh, Yury Y Ilinsky, Inga Yu Rauschenbach
The Forkhead BoxO transcription factor (FOXO) is a component of the insulin signalling pathway and plays a role in responding to adverse conditions, such as oxidative stress and starvation. In stressful conditions, FOXO moves from the cytosol to the nucleus where it activates gene expression programmes. Here, we show that FOXO in Drosophila melanogaster responds to heat stress as it does to other stressors. The catecholamine signalling pathway is another component of the stress response. In Drosophila, dopamine and octopamine levels rise steeply under heat, nutrition and mechanical stresses, which is followed by a decrease in the activity of synthesis enzymes...
October 17, 2016: Biology Open
Audrey Berthe, Stéphane Flament, Stéphanie Grandemange, Marie Zaffino, Michel Boisbrun, Sabine Mazerbourg
We have previously shown that Δ2-Troglitazone (Δ2-TGZ) displayed anticancer effects on breast cancer cell lines grown in low serum conditions (1% fetal calf serum (FCS)). The present study was performed in order to characterize the effects of Δ2-TGZ in high serum containing medium and to determine if starvation could influence the response of breast cancer cells to this compound, keeping in mind the potential interest for breast cancer therapy. We observed that in high serum conditions (10% FCS), a 48 h treatment with Δ2-TGZ induced a decrease in cell numbers in MDA-MB-231 and MCF-7 breast cancer cell lines...
October 18, 2016: Cell Cycle
Xuehua Shao, Duo Lai, Ling Zhang, Hanhong Xu
Azadirachtin is one of the most effective botanical insecticides and has been widely used in pest control. Toxicological reports show that azadirachtin can induce apoptosis in various insect cell lines. However, studies of azadirachtin-induced autophagy in cultured insect cells are lacking. This study reports that azadirachtin A significantly inhibits cell proliferation by inducing autophagic and apoptotic cell death in Spodoptera litura cultured cell line (SL-1 cell). Characteristic autophagolysosome and Atg8-PE (phosphatidylethanolamine) accumulation were observed by electron microscopy and western blotting, indicating that azadirachtin triggered autophagy in SL-1 cell...
October 18, 2016: Scientific Reports
Monique Mostert, Anthony Bonavia
BACKGROUND Besides providing anesthesia for surgery, the anesthesiologist's role is to optimize the patient for surgery and for post-surgical recovery. This involves timely identification and treatment of medical comorbidities and abnormal laboratory values that could complicate the patient's perioperative course. There are several potential causes of anion and non-anion gap metabolic acidosis in surgical patients, most of which could profoundly affect a patient's surgical outcome. Thus, the presence of an acute acid-base disturbance requires a thorough workup, the results of which will influence the patient's anesthetic management...
October 18, 2016: American Journal of Case Reports
Weifang Wu, Qin Deng, Pibiao Shi, Jinghua Yang, Zhongyuan Hu, Mingfang Zhang
Watermelon (Citrullus lanatus) is a globally important crop belonging to the family Cucurbitaceae. The grafting technique is commonly used to improve its tolerance to stress, as well as to enhance its nutrient uptake and utilization. It is believed that miRNA is most likely involved in its nutrient-starvation response as a graft-transportable signal. The quantitative real-time reverse transcriptase polymerase chain reaction is the preferred method for miRNA functional analysis, in which reliable reference genes for normalization are crucial to ensure the accuracy...
2016: PloS One
Avik Roy, Madhuchhanda Kundu, Malabendu Jana, Rama K Mishra, Yeni Yung, Chi-Hao Luan, Frank J Gonzalez, Kalipada Pahan
Peroxisome proliferator-activated receptor-α (PPARα) regulates hepatic fatty acid catabolism and mediates the metabolic response to starvation. Recently we found that PPARα is constitutively activated in nuclei of hippocampal neurons and controls plasticity via direct transcriptional activation of CREB. Here we report the discovery of three endogenous PPARα ligands-3-hydroxy-(2,2)-dimethyl butyrate, hexadecanamide, and 9-octadecenamide-in mouse brain hippocampus. Mass spectrometric detection of these compounds in mouse hippocampal nuclear extracts, in silico interaction studies, time-resolved FRET analyses, and thermal shift assay results clearly indicated that these three compounds served as ligands of PPARα...
October 17, 2016: Nature Chemical Biology
V Coothankandaswamy, S Cao, Y Xu, P D Prasad, P K Singh, C P Reynolds, S Yang, J Ogura, V Ganapathy, Y D Bhutia
BACKGROUND AND PURPOSE: Pancreatic cancer is an often lethal solid tumor. There is an urgent need to identify new drug targets for this disease. Highly proliferating cancer cells have an increased demand for nutrients and hence need to upregulate selective amino acid transporters. Here we wanted to find out which amino acid transporters are upregulated in pancreatic cancer and whether any of these transporters has potential as a drug target for this deadly disease. EXPERIMENTAL APPROACH: Expression of amino acid transporters in pancreatic cancer was analyzed using publicly available microarray datasets, and the findings with the transporter SLC6A14 were validated by mRNA and protein analysis...
October 17, 2016: British Journal of Pharmacology
Delyan R Mutavchiev, Marcin Leda, Kenneth E Sawin
The Rho family GTPase Cdc42 is a key regulator of eukaryotic cellular organization and cell polarity [1]. In the fission yeast Schizosaccharomyces pombe, active Cdc42 and associated effectors and regulators (the "Cdc42 polarity module") coordinate polarized growth at cell tips by controlling the actin cytoskeleton and exocytosis [2-4]. Localization of the Cdc42 polarity module to cell tips is thus critical for its function. Here we show that the fission yeast stress-activated protein kinase Sty1, a homolog of mammalian p38 MAP kinase, regulates localization of the Cdc42 polarity module...
October 1, 2016: Current Biology: CB
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