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https://www.readbyqxmd.com/read/29129818/inter-and-intra-subject-variability-of-nitric-oxide-levels-in-leukocyte-subpopulations
#1
Sheena Maharaj, Kim Lu, Shlomit Aizik, Frank Zaldivar, Fadia Haddad, Hye-Won Shin, Szu-Yun Leu, Eliezer Nussbaum, Inderpal Randhawa, Dan Cooper
Assessment of nitric oxide (NO) dynamics in immune cells, commonly measured using NO surrogates such as inducible nitric oxide synthase (iNOS) rather than NO itself, has been effective in understanding pathophysiology across a wide range of diseases. Although the intracellular measurement of NO is now feasible, many technical issues remain unresolved. The principle aim of our study was to determine the effect of storage time of whole blood on nitric oxide (NO) level expression in leukocytes. This is important because immune cells remain chemically dynamic even after they are removed from the circulation, and the impact of storage time must be known to optimally quantify the effect of a disease or condition on NO dynamics in circulating leukocytes...
November 9, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/29109437/mir-355-functions-as-an-important-link-between-p38-mapk-signaling-and-insulin-signaling-in-the-regulation-of-innate-immunity
#2
Lingtong Zhi, Yonglin Yu, Zhixia Jiang, Dayong Wang
We performed a systematic identification of microRNAs (miRNAs) involved in the control of innate immunity. We identified 7 novel miRNA mutants with altered survival, colony forming in the body, and expression pattern of putative antimicrobial genes after Pseudomonas aeruginosa infection. Loss-of-function mutation of mir-45, mir-75, mir-246, mir-256, or mir-355 induced resistance to P. aeruginosa infection, whereas loss-of-function mutation of mir-63 or mir-360 induced susceptibility to P. aeruginosa infection...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28959501/chaperone-directed-ubiquitylation-maintains-proteostasis-at-the-expense-of-longevity
#3
COMMENT
Wojciech Pokrzywa, Robin Lorenz, Thorsten Hoppe
The integrity of the cellular proteome is supported by quality control networks, which govern protein synthesis, folding, and degradation. It is generally accepted that an age-related decline in protein homeostasis (proteostasis) contributes to protein aggregation diseases. However, the mechanistic principles underlying proteostasis imbalance and the impact on life expectancy are not well understood. We recently demonstrated that this interrelation is affected by chaperone-directed ubiquitylation, shifting the amount of the conserved DAF-2/insulin receptor both in Caenorhabditis elegans and Drosophila melanogaster...
2017: Worm
https://www.readbyqxmd.com/read/28935419/red-near-infrared-light-stimulates-release-of-an-endothelium-dependent-vasodilator-and-rescues-vascular-dysfunction-in-a-diabetes-model
#4
Agnes Keszler, Brian Lindemer, Dorothee Weihrauch, Deron Jones, Neil Hogg, Nicole L Lohr
Peripheral artery disease (PAD) is a morbid condition whereby ischemic peripheral muscle causes pain and tissue breakdown. Interestingly, PAD risk factors, e.g. diabetes mellitus, cause endothelial dysfunction secondary to decreased nitric oxide (NO) levels, which could explain treatment failures. Previously, we demonstrated 670nm light (R/NIR) increased NO from nitrosyl-heme stores, therefore we hypothesized R/NIR can stimulate vasodilation in healthy and diabetic blood vessels. Vasodilation was tested by ex vivo pressure myography in wild type C57Bl/6, endothelial nitric oxide synthase (eNOS) knockout, and db/db mice (10mW/cm(2) for 5min with 10min dark period)...
September 19, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28934747/untangling-longevity-dauer-and-healthspan-in-caenorhabditis-elegans-insulin-igf-1-signalling
#5
Collin Yvès Ewald, Jorge Iván Castillo-Quan, T Keith Blackwell
The groundbreaking discovery that lower levels of insulin/IGF-1 signaling (IIS) can induce lifespan extension was reported 24 years ago in the nematode Caenorhabditis elegans. In this organism, mutations in the insulin/IGF-1 receptor gene daf-2 or other genes in this pathway can double lifespan. Subsequent work has revealed that reduced IIS (rIIS) extends lifespan across diverse species, possibly including humans. In C. elegans, IIS also regulates development into the diapause state known as dauer, a quiescent larval form that enables C...
September 22, 2017: Gerontology
https://www.readbyqxmd.com/read/28912066/the-camp-effectors-pka-and-epac-activate-endothelial-no-synthase-through-pi3k-akt-pathway-in-human-endothelial-cells
#6
Verónica García-Morales, María Luaces-Regueira, Manuel Campos-Toimil
3',5'-Cyclic adenosine monophosphate (cAMP) exerts an endothelium-dependent vasorelaxant action by stimulating endothelial NO synthase (eNOS) activity, and the subsequent NO release, through cAMP protein kinase (PKA) and exchange protein directly activated by cAMP (Epac) activation in endothelial cells. Here, we have investigated the mechanism by which the cAMP-Epac/PKA pathway activates eNOS. cAMP-elevating agents (forskolin and dibutyryl-cAMP) and the joint activation of PKA (6-Bnz-cAMP) and Epac (8-pCPT-2'-O-Me-cAMP) increased cytoplasmic Ca(2+) concentration ([Ca(2+)]c) in ≤30% of fura-2-loaded isolated human umbilical vein endothelial cells (HUVEC)...
September 11, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28900141/dianxianning-improved-amyloid-%C3%AE-induced-pathological-characteristics-partially-through-daf-2-daf-16-insulin-like-pathway-in-transgenic-c-elegans
#7
Dejuan Zhi, Dong Wang, Wenqi Yang, Ziyun Duan, Shuqian Zhu, Juan Dong, Na Wang, Ningbo Wang, Dongqing Fei, Zhanxin Zhang, Xin Wang, Meizhu Wang, Hongyu Li
Dianxianning (DXN) is a traditional Chinese formula, and has been approved in China for treating epilepsy since 1996. Here anti-Alzheimer's disease activity of DXN has been reported. DXN improved AD-like symptoms of paralysis and 5-HT sensitivity of transgenic Aβ1-42 C. elegans. In worms, DXN significantly increased Aβ monomers and decreased the toxic Aβ oligomers, thus reducing Aβ toxicity. DXN significantly suppressed the expression of hsp-16.2 induced by juglone, and up-regulated sod-3 expression. These results indicated that DXN increased stress resistance and protected C...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28872980/the-recycling-endosome-protein-rab-10-promotes-autophagic-flux-and-localization-of-the-transmembrane-protein-atg-9
#8
N J Palmisano, N Rosario, M Wysocki, M Hong, B Grant, A Meléndez
Macroautophagy/autophagy involves the formation of an autophagosome, a double-membrane vesicle that delivers sequestered cytoplasmic cargo to lysosomes for degradation and recycling. Closely related, endocytosis mediates the sorting and transport of cargo throughout the cell, and both processes are important for cellular homeostasis. However, how endocytic proteins functionally intersect with autophagy is not clear. Mutations in the DAF-2/insulin-like IGF-1 (INSR) receptor at the permissive temperature result in a small increase in GFP::LGG-1 foci, i...
October 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28820880/knock-out-of-a-mitochondrial-sirtuin-protects-neurons-from-degeneration-in-caenorhabditis-elegans
#9
Rachele Sangaletti, Massimo D'Amico, Jeff Grant, David Della-Morte, Laura Bianchi
Sirtuins are NAD⁺-dependent deacetylases, lipoamidases, and ADP-ribosyltransferases that link cellular metabolism to multiple intracellular pathways that influence processes as diverse as cell survival, longevity, and cancer growth. Sirtuins influence the extent of neuronal death in stroke. However, different sirtuins appear to have opposite roles in neuronal protection. In Caenorhabditis elegans, we found that knock-out of mitochondrial sirtuin sir-2.3, homologous to mammalian SIRT4, is protective in both chemical ischemia and hyperactive channel induced necrosis...
August 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28817671/immunohistochemical-analysis-reveals-variations-in-proteasome-tissue-expression-in-c-elegans
#10
Elisa Mikkonen, Caj Haglund, Carina I Holmberg
The ubiquitin-proteasome system (UPS) plays a crucial part in normal cell function by mediating intracellular protein clearance. We have previously shown that UPS-mediated protein degradation varies in a cell type-specific manner in C. elegans. Here, we use formalin-fixed, paraffin-embedded C. elegans sections to enable studies on endogenous proteasome tissue expression. We show that the proteasome immunoreactivity pattern differs between cell types and within subcellular compartments in adult wild-type (N2) C...
2017: PloS One
https://www.readbyqxmd.com/read/28723894/cysteine-protease-cathepsin-b-mediates-radiation-induced-bystander-effects
#11
Yu Peng, Man Zhang, Lingjun Zheng, Qian Liang, Hanzeng Li, Jeng-Ting Chen, Hongyan Guo, Sawako Yoshina, Yu-Zen Chen, Xiang Zhao, Xiaoqi Wu, Bin Liu, Shohei Mitani, Jau-Song Yu, Ding Xue
The radiation-induced bystander effect (RIBE) refers to a unique process in which factors released by irradiated cells or tissues exert effects on other parts of the animal not exposed to radiation, causing genomic instability, stress responses and altered apoptosis or cell proliferation. Although RIBEs have important implications for radioprotection, radiation safety and radiotherapy, the molecular identities of RIBE factors and their mechanisms of action remain poorly understood. Here we use Caenorhabditis elegans as a model in which to study RIBEs, and identify the cysteine protease CPR-4, a homologue of human cathepsin B, as the first RIBE factor in nematodes, to our knowledge...
July 27, 2017: Nature
https://www.readbyqxmd.com/read/28700905/chronic-iron-overload-induces-functional-and-structural-vascular-changes-in-small-resistance-arteries-via-nadph-oxidase-dependent-o2-production
#12
Rogério Faustino Ribeiro Júnior, Vinicius Bermond Marques, Dieli Oliveira Nunes, Ivanita Stefanon, Leonardo Dos Santos
Iron overload leads to excessive free radical formation and induces cardiovascular dysfunction. Thus, our aim was to investigate the structural and endothelial modulation of vascular tone induced by chronic iron overload in mesenteric arteries. Rats were divided into two groups: the control (vehicle) group and the group treated with iron dextran for 28days (100mg/kg, 5days a week). Chronic iron overload altered the following morpho-physiological parameters of third-order mesenteric resistance arteries: decreased lumen and external diameters; increased wall/lumen ratio and wall thickness; decreased distensibility and increased stiffness; and increased pulse wave velocity...
September 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28675140/spatiotemporal-regulation-of-autophagy-during-caenorhabditis-elegans-aging
#13
Jessica T Chang, Caroline Kumsta, Andrew B Hellman, Linnea M Adams, Malene Hansen
Autophagy has been linked to longevity in many species, but the underlying mechanisms are unclear. Using a GFP-tagged and a new tandem-tagged Atg8/LGG-1 reporter, we quantified autophagic vesicles and performed autophagic flux assays in multiple tissues of wild-type Caenorhabditis elegans and long-lived daf-2/insulin/IGF-1 and glp-1/Notch mutants throughout adulthood. Our data are consistent with an age-related decline in autophagic activity in the intestine, body-wall muscle, pharynx, and neurons of wild-type animals...
July 4, 2017: ELife
https://www.readbyqxmd.com/read/28627510/glycogen-controls-caenorhabditis-elegans-lifespan-and-resistance-to-oxidative-stress
#14
Ivan Gusarov, Bibhusita Pani, Laurent Gautier, Olga Smolentseva, Svetlana Eremina, Ilya Shamovsky, Olga Katkova-Zhukotskaya, Alexander Mironov, Evgeny Nudler
A high-sugar diet has been associated with reduced lifespan in organisms ranging from worms to mammals. However, the mechanisms underlying the harmful effects of glucose are poorly understood. Here we establish a causative relationship between endogenous glucose storage in the form of glycogen, resistance to oxidative stress and organismal aging in Caenorhabditis elegans. We find that glycogen accumulated on high dietary glucose limits C. elegans longevity. Glucose released from glycogen and used for NADPH/glutathione reduction renders nematodes and human hepatocytes more resistant against oxidative stress...
June 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28620088/the-r148-3-gene-modulates-caenorhabditis-elegans-lifespan-and-fat-metabolism
#15
Catherine Roy-Bellavance, Jennifer M Grants, Stéphanie Miard, Kayoung Lee, Évelyne Rondeau, Chantal Guillemette, Martin J Simard, Stefan Taubert, Frédéric Picard
Despite many advances, the molecular links between energy metabolism and longevity are not well understood. Here, we have used the nematode model Caenorhabditis elegans to study the role of the yet-uncharacterized gene R148.3 in fat accumulation and lifespan. In wild-type worms, a R148.3p::GFP reporter showed enhanced expression throughout life in the pharynx, in neurons, and in muscles. Functionally, a protein fusing a predicted 22 amino acid N-terminal signal sequence (SS) of R148.3 to mCherry displayed robust accumulation in coelomyocytes, indicating that R148...
August 7, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28576866/heat-induced-calcium-leakage-causes-mitochondrial-damage-in-caenorhabditis-elegans-body-wall-muscles
#16
Kenta Momma, Takashi Homma, Ruri Isaka, Surabhi Sudevan, Atsushi Higashitani
Acute onset of organ failure in heatstroke is triggered by rhabdomyolysis of skeletal muscle. Here, we showed that elevated temperature increases free cytosolic Ca(2+) [Ca(2+)]f from RYR (ryanodine receptor)/UNC-68 in vivo in the muscles of an experimental model animal, the nematode Caenorhabditis elegans This subsequently leads to mitochondrial fragmentation and dysfunction, and breakdown of myofilaments similar to rhabdomyolysis. In addition, treatment with an inhibitor of RYR (dantrolene) or activation of FoxO (Forkhead box O)/DAF-16 is effective against heat-induced muscle damage...
August 2017: Genetics
https://www.readbyqxmd.com/read/28576774/the-fusogen-aff-1-can-rejuvenate-the-regenerative-potential-of-adult-dendritic-trees-by-self-fusion
#17
Veronika Kravtsov, Meital Oren-Suissa, Benjamin Podbilewicz
The aging brain undergoes structural changes that affect brain homeostasis, neuronal function and consequently cognition. The complex architecture of dendritic arbors poses a challenge to understanding age-dependent morphological alterations, behavioral plasticity and remodeling following brain injury. Here, we use the PVD polymodal neurons of C. elegans as a model to study how aging affects neuronal plasticity. Using confocal live imaging of C. elegans PVD neurons, we demonstrate age-related progressive morphological alterations of intricate dendritic arbors...
July 1, 2017: Development
https://www.readbyqxmd.com/read/28576337/angiostrongylus-cantonensis-daf-2-regulates-dauer-longevity-and-stress-in-caenorhabditis-elegans
#18
Baolong Yan, Weiwei Sun, Xiaomeng Shi, Liyang Huang, Lingzi Chen, Suhua Wang, Lanzhu Yan, Shaohui Liang, Huicong Huang
The insulin-like signaling (IIS) pathway is considered to be significant in regulating fat metabolism, dauer formation, stress response and longevity in Caenorhabditis elegans. "Dauer hypothesis" indicates that similar IIS transduction mechanism regulates dauer development in free-living nematode C. elegans and the development of infective third-stage larvae (iL3) in parasitic nematodes, and this is bolstered by a few researches on structures and functions of the homologous genes in the IIS pathway cloned from several parasitic nematodes...
June 15, 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/28562327/the-protein-kinase-mbk-1-contributes-to-lifespan-extension-in-daf-2-mutant-and-germline-deficient-caenorhabditis-elegans
#19
Hildegard I D Mack, Peichuan Zhang, Bryan R Fonslow, John R Yates
In Caenorhabditis elegans, reduction of insulin/IGF-1 like signaling and loss of germline stem cells both increase lifespan by activating the conserved transcription factor DAF-16 (FOXO). While the mechanisms that regulate DAF-16 nuclear localization in response to insulin/IGF-1 like signaling are well characterized, the molecular pathways that act in parallel to regulate DAF-16 transcriptional activity, and the pathways that couple DAF-16 activity to germline status, are not fully understood at present. Here, we report that inactivation of MBK-1, the C...
May 25, 2017: Aging
https://www.readbyqxmd.com/read/28484701/dual-specificity-phosphatase-4-overexpression-in-cells-prevents-hypoxia-reoxygenation-induced-apoptosis-via-the-upregulation-of-enos
#20
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
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