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https://www.readbyqxmd.com/read/28484701/dual-specificity-phosphatase-4-overexpression-in-cells-prevents-hypoxia-reoxygenation-induced-apoptosis-via-the-upregulation-of-enos
#1
Julie A Dougherty, Joanna Kilbane Myers, Mahmood Khan, Mark G Angelos, Chun-An Chen
Mitogen-activated protein kinases (MAPKs) signaling cascades regulate several cellular functions, including differentiation, proliferation, survival, and apoptosis. The duration and magnitude of phosphorylation of these MAPKs are decisive determinants of their physiological functions. Dual-specificity phosphatases exert kinetic control over these signaling cascades. Previously, we demonstrated that DUSP4(-/-) hearts sustain a larger infarct and have poor functional recovery, when isolated hearts were subjected to ischemia/reperfusion...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28441527/proteostasis-or-aging-let-the-chips-fall-where-they-may
#2
Robyn Branicky, Siegfried Hekimi
The conserved E3 ubiquitin ligase CHIP/CHN-1 contributes to proteostasis by ubiquitylating HSP70 and HSP90-interacting proteins. In a recent issue of Cell,Tawo et al. (2017) show that CHIP/CHN-1 also directly ubiquitylates the insulin receptor INSR/DAF-2 to regulate its turnover. These findings suggest an unexpected interpretation of the effects of altered proteostasis on survival.
April 24, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28434978/calycosin-promotes-lifespan-in-caenorhabditis-elegans-through-insulin-signaling-pathway-via-daf-16-age-1-and-daf-2
#3
Lulu Lu, Xuan Zhao, Jianyong Zhang, Miao Li, Yonghao Qi, Lijun Zhou
The naturally occurring calycosin is a known antioxidant that prevents redox imbalance in organisms. However, calycosin's effect on lifespan and its physiological molecular mechanisms are not yet well understood. In this study, we demonstrated that calycosin could prolong the lifespan of Caenorhabditiselegans, and that such extension was associated with its antioxidant capability as well as its ability to enhance stress resistance and reduce ROS (reactive oxygen species) accumulation. To explore mechanisms of this longevity effect, we assessed the impact of calycosin on lifespans of insulin-signaling impaired worms: daf-2, age-1, and daf-16 mutants...
April 20, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28423308/how-a-mutation-that-slows-aging-can-also-disproportionately-extend-end-of-life-decrepitude
#4
Katie Podshivalova, Rex A Kerr, Cynthia Kenyon
The goal of aging research is to extend healthy, active life. For decades, C. elegans daf-2 insulin/insulin-like growth factor 1 (IGF-1) receptor mutants have served as a model for extended lifespan and youthfulness. However, a recent report suggested that their longevity is associated with an undesirable phenotype: a disproportionately long period of decrepitude at the end of life. In the human population, such an outcome would be a burden to society, bringing into question the relevance of daf-2 mutants as a model for life extension...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28366735/regulator-of-g-protein-signaling-1-modulates-paraquat-induced-oxidative-stress-and-longevity-via-the-insulin-like-signaling-pathway-in-caenorhabditis-elegans
#5
Mingyu Wu, Xin Kang, Qiang Wang, Chunyu Zhou, Chandra Mohan, Ai Peng
Insulin or insulin like signaling (IIS) pathway is a crucial pathway in Caenorhabditis elegans associated with mediating longevity, and stress resistance. Regulators of G protein signaling (RGS) also modulate stress resistance and longevity in multiple in vitro and in vivo models. However, the mechanism underlying RGS mediating stress resistance and longevity remains largely unclear. Here we report that rgs-1, an important member of rgs family, is a novel modulator of IIS pathway in C. elegans. We found that the loss of rgs-1 dramatically promoted paraquat resistance in C...
May 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28285998/a-non-cell-autonomous-role-of-bec-1-becn1-beclin1-in-coordinating-cell-cycle-progression-and-stem-cell-proliferation-during-germline-development
#6
Kristina Ames, Dayse S Da Cunha, Brenda Gonzalez, Marina Konta, Feng Lin, Gabriel Shechter, Lev Starikov, Sara Wong, Hannes E Bülow, Alicia Meléndez
The decision of stem cells to proliferate and differentiate is finely controlled. The Caenorhabditis elegans germline provides a tractable system for studying the mechanisms that control stem cell proliferation and homeostasis [1-4]. Autophagy is a conserved cellular recycling process crucial for cellular homeostasis in many different contexts [5], but its function in germline stem cell proliferation remains poorly understood. Here, we describe a function for autophagy in germline stem cell proliferation. We found that autophagy genes such as bec-1/BECN1/Beclin1, atg-16...
March 20, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28276441/rna-surveillance-via-nonsense-mediated-mrna-decay-is-crucial-for-longevity-in-daf-2-insulin-igf-1-mutant-c-elegans
#7
Heehwa G Son, Mihwa Seo, Seokjin Ham, Wooseon Hwang, Dongyeop Lee, Seon Woo A An, Murat Artan, Keunhee Seo, Rachel Kaletsky, Rachel N Arey, Youngjae Ryu, Chang Man Ha, Yoon Ki Kim, Coleen T Murphy, Tae-Young Roh, Hong Gil Nam, Seung-Jae V Lee
Long-lived organisms often feature more stringent protein and DNA quality control. However, whether RNA quality control mechanisms, such as nonsense-mediated mRNA decay (NMD), which degrades both abnormal as well as some normal transcripts, have a role in organismal aging remains unexplored. Here we show that NMD mediates longevity in C. elegans strains with mutations in daf-2/insulin/insulin-like growth factor 1 receptor. We find that daf-2 mutants display enhanced NMD activity and reduced levels of potentially aberrant transcripts...
March 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28209779/a-histone-h4-lysine-20-methyltransferase-couples-environmental-cues-to-sensory-neuron-control-of-developmental-plasticity
#8
Colin E Delaney, Albert T Chen, Jacqueline V Graniel, Kathleen J Dumas, Patrick J Hu
Animals change developmental fates in response to external cues. In the nematode Caenorhabditis elegans, unfavorable environmental conditions induce a state of diapause known as dauer by inhibiting the conserved DAF-2 insulin-like signaling (ILS) pathway through incompletely understood mechanisms. We have previously established a role for the C. elegans dosage compensation protein DPY-21 in the control of dauer arrest and DAF-2 ILS. Here, we show that the histone H4 lysine 20 methyltransferase SET-4, which also influences dosage compensation, promotes dauer arrest in part by repressing the X-linked ins-9 gene, which encodes a new agonist insulin-like peptide (ILP) expressed specifically in the paired ASI sensory neurons that are required for dauer bypass...
April 1, 2017: Development
https://www.readbyqxmd.com/read/28181396/the-aflatoxin-b1-fumonisin-b1-toxicity-in-brl-3a-hepatocytes-is-associated-to-induction-of-cytochrome-p450-activity-and-arachidonic-acid-metabolism
#9
Verónica S Mary, Silvina L Arias, Santiago N Otaiza, Pilar A Velez, Héctor R Rubinstein, Martín G Theumer
Human oral exposure to aflatoxin B1 (AFB1 ) and fumonisin B1 (FB1 ) is associated with increased hepatocellular carcinoma. Although evidence suggested interactive AFB1 -FB1 hepatotoxicity, the underlying mechanisms remain mostly unidentified. This work was aimed at evaluating the possible AFB1 -FB1 interplay to induce genetic and cell cycle toxicities in BRL-3A rat hepatocytes, reactive oxygen species (ROS) involvement, and the AFB1 metabolizing pathways cytochrome P450 (CYP) and arachidonic acid (ArAc) metabolism as ROS contributors...
June 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28134244/bacillus-subtilis-biofilm-extends-caenorhabditis-elegans-longevity-through-downregulation-of-the-insulin-like-signalling-pathway
#10
Verónica Donato, Facundo Rodríguez Ayala, Sebastián Cogliati, Carlos Bauman, Juan Gabriel Costa, Cecilia Leñini, Roberto Grau
Beneficial bacteria have been shown to affect host longevity, but the molecular mechanisms mediating such effects remain largely unclear. Here we show that formation of Bacillus subtilis biofilms increases Caenorhabditis elegans lifespan. Biofilm-proficient B. subtilis colonizes the C. elegans gut and extends worm lifespan more than biofilm-deficient isogenic strains. Two molecules produced by B. subtilis - the quorum-sensing pentapeptide CSF and nitric oxide (NO) - are sufficient to extend C. elegans longevity...
January 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28131844/mas-receptor-is-involved-in-the-estrogen-receptor-induced-nitric-oxide-dependent-vasorelaxation
#11
Agua Sobrino, Susana Vallejo, Susana Novella, Macarena Lázaro-Franco, Ana Mompeón, Carlos Bueno-Betí, Thomas Walther, Carlos Sánchez-Ferrer, Concepción Peiró, Carlos Hermenegildo
The Mas receptor is involved in the angiotensin (Ang)-(1-7) vasodilatory actions by increasing nitric oxide production (NO). We have previously demonstrated an increased production of Ang-(1-7) in human umbilical vein endothelial cells (HUVEC) exposed to estradiol (E2), suggesting a potential cross-talk between E2 and the Ang-(1-7)/Mas receptor axis. Here, we explored whether the vasoactive response and NO-related signalling exerted by E2 are influenced by Mas. HUVEC were exposed to 10nM E2 for 24h in the presence or absence of the selective Mas receptor antagonist A779, and the estrogen receptor (ER) antagonist ICI182780 (ICI)...
April 1, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28076789/reduced-insulin-igf-1-signaling-restores-the-dynamic-properties-of-key-stress-granule-proteins-during-aging
#12
Marie C Lechler, Emily D Crawford, Nicole Groh, Katja Widmaier, Raimund Jung, Janine Kirstein, Jonathan C Trinidad, Alma L Burlingame, Della C David
Low-complexity "prion-like" domains in key RNA-binding proteins (RBPs) mediate the reversible assembly of RNA granules. Individual RBPs harboring these domains have been linked to specific neurodegenerative diseases. Although their aggregation in neurodegeneration has been extensively characterized, it remains unknown how the process of aging disturbs RBP dynamics. We show that a wide variety of RNA granule components, including stress granule proteins, become highly insoluble with age in C. elegans and that reduced insulin/insulin-like growth factor 1 (IGF-1) daf-2 receptor signaling efficiently prevents their aggregation...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/27997907/improvement-of-huangqi-decoction-on-endothelial-dysfunction-in-5-6-nephrectomized-rats
#13
Shuang Chu, Li Wang, Xiao-Dong Mao, Wen Peng
BACKGROUND/AIMS: Endothelial dysfunction is a major factor in the progression of chronic kidney disease, which correlates with oxidative stress and NO deficiency. Huangqi decoction (HQD) is a potential anti-oxidant ingredient in renoprotection. However, the underlying mechanisms remained identified. Therefore, we investigated whether HQD exhibit improvement in endothelial dysfunction in the 5/6 nephrectomy (Nx) rat model. METHODS: Male Wistar rats (180 - 250 g) were divided into sham, Nx and Nx + HQD (0...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27989925/cholesterol-regulates-daf-16-nuclear-localization-and-fasting-induced-longevity-in-c-elegans
#14
Akiko Ihara, Masaharu Uno, Koichi Miyatake, Sakiko Honjoh, Eisuke Nishida
Cholesterol has attracted significant attention as a possible lifespan regulator. It has been reported that serum cholesterol levels have an impact on mortality due to age-related disorders such as cardiovascular disease. Diet is also known to be an important lifespan regulator. Dietary restriction retards the onset of age-related diseases and extends lifespan in various organisms. Although cholesterol and dietary restriction are known to be lifespan regulators, it remains to be established whether cholesterol is involved in dietary restriction-induced longevity...
January 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/27989695/the-genetics-of-isoflurane-induced-developmental-neurotoxicity
#15
Hyo-Seok Na, Nicole L Brockway, Katherine R Gentry, Elyce Opheim, Margaret M Sedensky, Philip G Morgan
INTRODUCTION: Neurotoxicity induced by early developmental exposure to volatile anesthetics is a characteristic of organisms across a wide range of species, extending from the nematode C. elegans to mammals. Prevention of anesthetic-induced neurotoxicity (AIN) will rely upon an understanding of its underlying mechanisms. However, no forward genetic screens have been undertaken to identify the critical pathways affected in AIN. By characterizing such pathways, we may identify mechanisms to eliminate isoflurane induced AIN in mammals...
March 2017: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27958277/a-genome-wide-screen-of-bacterial-mutants-that-enhance-dauer-formation-in-c-elegans
#16
Amit Khanna, Jitendra Kumar, Misha A Vargas, LaKisha Barrett, Subhash Katewa, Patrick Li, Tom McCloskey, Amit Sharma, Nicole Naudé, Christopher Nelson, Rachel Brem, David W Killilea, Sean D Mooney, Matthew Gill, Pankaj Kapahi
Molecular pathways involved in dauer formation, an alternate larval stage that allows Caenorhabditis elegans to survive adverse environmental conditions during development, also modulate longevity and metabolism. The decision to proceed with reproductive development or undergo diapause depends on food abundance, population density, and temperature. In recent years, the chemical identities of pheromone signals that modulate dauer entry have been characterized. However, signals derived from bacteria, the major source of nutrients for C...
December 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27884946/analysis-of-the-caenorhabditis-elegans-innate-immune-response-to-coxiella-burnetii
#17
James M Battisti, Lance A Watson, Myo T Naung, Adam M Drobish, Ekaterina Voronina, Michael F Minnick
The nematode Caenorhabditis elegans is well established as a system for characterization and discovery of molecular mechanisms mediating microbe-specific inducible innate immune responses to human pathogens. Coxiella burnetii is an obligate intracellular bacterium that causes a flu-like syndrome in humans (Q fever), as well as abortions in domesticated livestock, worldwide. Initially, when wild type C. elegans (N2 strain) was exposed to mCherry-expressing C. burnetii (CCB) a number of overt pathological manifestations resulted, including intestinal distension, deformed anal region and a decreased lifespan...
February 2017: Innate Immunity
https://www.readbyqxmd.com/read/27884734/nitric-oxide-coupled-signaling-in-odor-elicited-molecular-events-in-the-olfactory-center-of-the-terrestrial-snail-helix-pomatia
#18
Zoltán Serfőző, Kálmán Nacsa, Zoltán Veréb, Izabella Battonyai, Csaba Hegedűs, Csilla Balogh, Károly Elekes
Olfaction, a chemosensory modality, plays a pivotal role in the orientation and behavior of invertebrates. The central olfactory processing unit in terrestrial stylomatophoran snails is the procerebrum, which contains NO synthesizing interneurons, whose oscillatory currents are believed to be the base of odor evoked memory formation. Nevertheless, in this model the up- and downstream events of molecular cascades that trigger and follow NO release, respectively, have not been studied. Immunocytochemistry and flow cytometry studies performed on procerebral neural perikarya isolated from the snail Helix pomatia revealed cell populations with discrete DAF-2 fluorescence, indicating the release of different amounts of NO...
January 2017: Cellular Signalling
https://www.readbyqxmd.com/read/27856697/caenorhabditis-elegans-daf-2-as-a-model-for-human-insulin-receptoropathies
#19
David A Bulger, Tetsunari Fukushige, Sijung Yun, Robert K Semple, John A Hanover, Michael W Krause
Human exome sequencing has dramatically increased the rate of identification of disease-associated polymorphisms. However, examining the functional consequences of those variants has created an analytic bottleneck. Insulin-like signaling in Caenorhabditis elegans has long provided a model to assess consequences of human insulin signaling mutations, but this has not been evaluated in the context of current genetic tools. We have exploited strains derived from the Million Mutation Project (MMP) and gene editing to explore further the evolutionary relationships and conservation between the human and C...
January 5, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/27854075/benzimidazole-derivative-m084-extends-the-lifespan-of-caenorhabditis-elegans-in-a-daf-16-foxo-dependent-way
#20
Ai-Jun Ding, Gui-Sheng Wu, Bin Tang, Xuechuan Hong, Michael X Zhu, Huai-Rong Luo
With the growth of aging population, there is increasing demand to develop strategy to improve the aging process and aging-related diseases. Benzimidazole and its derivatives are crucial heterocyclic backbone of many drugs and compounds with diverse therapeutic applications, including alleviation of aging-related diseases. Here, we investigate if the benzimidazole derivative n-butyl-[1H]-benzimidazol-2-amine (M084), a novel inhibitor of TRPC4 and TRPC5 channels and antidepressant, could affect the lifespan of Caenorhabditis elegans (C...
February 2017: Molecular and Cellular Biochemistry
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