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oxidative stress and the diaphragm

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https://www.readbyqxmd.com/read/28177129/role-of-parp-activity-in-lung-cancer-induced-cachexia-effects-on-muscle-oxidative-stress-proteolysis-anabolic-markers-and-phenotype
#1
Alba Chacon-Cabrera, Mercè Mateu-Jimenez, Klaus Langohr, Clara Fermoselle, Elena García-Arumí, Antoni L Andreu, Jose Yelamos, Esther Barreiro
Strategies to treat cachexia are still at its infancy. Enhanced muscle protein breakdown and ubiquitin-proteasome system are common features of cachexia associated with chronic conditions including lung cancer (LC). Poly(ADP-ribose) polymerases (PARP), which play a major role in chromatin structure regulation, also underlie maintenance of muscle metabolism and body composition. We hypothesized that protein catabolism, proteolytic markers, muscle fiber phenotype, and muscle anabolism may improve in respiratory and limb muscles of LC-cachectic Parp-1-deficient (Parp-1(-/-) ) and Parp-2(-/-) mice...
February 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28152009/superoxide-dismutase-catalase-mimetic-euk-134-prevents-diaphragm-muscle-weakness-in-monocrotalin-induced-pulmonary-hypertension
#2
Koichi Himori, Masami Abe, Daisuke Tatebayashi, Jaesik Lee, Håkan Westerblad, Johanna T Lanner, Takashi Yamada
Patients with pulmonary hypertension (PH) suffer from inspiratory insufficiency, which has been associated with intrinsic contractile dysfunction in diaphragm muscle. Here, we examined the role of redox stress in PH-induced diaphragm weakness by using the novel antioxidant, EUK-134. Male Wistar rats were randomly divided into control (CNT), CNT + EUK-134 (CNT + EUK), monocrotaline-induced PH (PH), and PH + EUK groups. PH was induced by a single intraperitoneal injection of monocrotaline (60 mg/kg body weight)...
2017: PloS One
https://www.readbyqxmd.com/read/28056568/in-vitro-metabolite-formation-in-human-hepatocytes-and-cardiomyocytes-and-metabolism-and-tissue-distribution-in-monkeys-of-the-2-c-methylguanosine-prodrug-bms-986094
#3
Wenying Li, Kevin J Trouba, Li Ma, Jae Kwagh, Christopher Storck, Yongxin Zhu, Oliver Flint, William G Humphreys, Jian Wang, Ang Liu, Bonnie Wang, Michael J Graziano, Marc H Davies, Thomas P Sanderson
BMS-986094, a 2'-C-methylguanosine prodrug for the treatment of chronic hepatitis C virus infection, was withdrawn from phase 2 clinical trials because of unexpected cardiac and renal toxicities. To better understand these toxicities, the in vitro metabolism of BMS-986094 in human hepatocytes (HHs) and human cardiomyocytes (HCMs) and the measurement of BMS-986094 and selected metabolites in monkey plasma and tissues were assessed. BMS-986094 was extensively metabolized by HHs and HCMs, resulting in more efficient formation and accumulation of the active triphosphorylated metabolite, INX-09114, and less efficient efflux of metabolites in HCMs...
January 1, 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/28009790/exercise-training-reverses-extrapulmonary-impairments-in-smoke-exposed-mice
#4
T Scott Bowen, Lars Aakerøy, Sophia Eisenkolb, Patricia Kunth, Fredrik Bakkerud, Martin Wohlwend, Anne Marie Ormbostad, Tina Fischer, Ulrik Wisloff, Gerhard Schuler, Sigurd Steinshamn, Volker Adams, Eivind Bronstad
PURPOSE: Cigarette smoking is the main risk factor for chronic obstructive pulmonary disease and emphysema. However, evidence on the extrapulmonary effects of smoke exposure that precede lung impairments remains unclear at present, as are data on non-pharmacological treatments such as exercise training. METHODS: Three groups of mice including control (n=10), smoking (n=10), and smoking with 6 weeks of high-intensity interval treadmill running (n=11) were exposed to 20 weeks of fresh air or whole-body cigarette smoke...
December 22, 2016: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/27891095/differential-rna-expression-profile-of-skeletal-muscle-induced-by-experimental-autoimmune-myasthenia-gravis-in-rats
#5
Henry J Kaminski, Keiichi Himuro, Jumana Alshaikh, Bendi Gong, Georgiana Cheng, Linda L Kusner
The differential susceptibility of skeletal muscle by myasthenia gravis (MG) is not well understood. We utilized RNA expression profiling of extraocular muscle (EOM), diaphragm (DIA), and extensor digitorum (EDL) of rats with experimental autoimmune MG (EAMG) to evaluate the hypothesis that muscles respond differentially to injury produced by EAMG. EAMG was induced in female Lewis rats by immunization with acetylcholine receptor purified from the electric organ of the Torpedo. Six weeks later after rats had developed weakness and serum antibodies directed against the AChR, animals underwent euthanasia and RNA profiling performed on DIA, EDL, and EOM...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27812762/minimal-change-nephrotic-syndrome-and-prohibitin-2-gene-polymorphism
#6
Keisuke Sugimoto, Tomoki Miyazawa, Kohei Miyazaki, Hidehiko Yanagida, Takuji Enya, Hitomi Nishi, Norihisa Wada, Mitsuru Okada, Tsukasa Takemura
BACKGROUND: Patients with minimal change nephrotic syndrome (MCNS) often also have allergic diseases. Abnormalities of Th2-derived cytokines and T-cell functions contribute to development of these diseases. On the other hand, imbalances between reactive oxygen species (ROS) and antioxidants have been implicated in MCNS and progression of atopic dermatitis. ROS, produced mainly within mitochondria, subject cells to oxidative stress, while prohibitin 2 protects mitochondria by increasing tolerance to ROS...
November 4, 2016: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/27784315/intraoperative-hemidiaphragm-electrical-stimulation-reduces-oxidative-stress-and-upregulates-autophagy-in-surgery-patients-undergoing-mechanical-ventilation-exploratory-study
#7
Robert T Mankowski, Shakeel Ahmed, Thomas Beaver, Marvin Dirain, Chul Han, Phillip Hess, Tomas Martin, Barbara K Smith, Shinichi Someya, Christiaan Leeuwenburgh, A Daniel Martin
BACKGROUND: Mechanical ventilation (MV) during a cardio-thoracic surgery contributes to diaphragm muscle dysfunction that impairs weaning and can lead to the ventilator- induced diaphragm dysfunction. Especially, it is critical in older adults who have lower muscle reparative capacity following MV. Reports have shown that the intraoperative intermittent hemidiaphragm electrical stimulation can maintain and/or improve post-surgery diaphragm function. In particular, from a molecular point of view, intermittent ES may reduce oxidative stress and increase regulatory autophagy levels, and therefore improve diaphragm function in animal studies...
October 26, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27666779/exploring-spinal-cord-protection-by-remote-ischemic-preconditioning-an-experimental-study
#8
Johanna Herajärvi, Tuomas Anttila, Henna Sarja, Caius Mustonen, Henri Haapanen, Tuomas Mäkelä, Fredrik Yannopoulos, Tuomo Starck, Mika Kallio, Hannu Tuominen, Ulla Puistola, Peeter Karihtala, Kai Kiviluoma, Vesa Anttila, Tatu Juvonen
BACKGROUND: Paraplegia is one of the most severe complications occurring after the repair of thoracic and thoracoabdominal aortic aneurysms. Remote ischemic preconditioning (RIPC) has been shown to mitigate neurologic damage, and this study assessed its efficacy in preventing spinal cord ischemia. METHODS: The study randomized 16 female pigs into an RIPC group (n = 8) and a control group (n = 8). The RIPC group underwent four cycles of 5-minute ischemia-reperfusion episodes by intermittent occlusion of the left iliac artery...
September 22, 2016: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/27662602/role-of-protein-kinase-g-and-reactive-oxygen-species-in-the-regulation-of-podocyte-function-in-health-and-disease
#9
REVIEW
Agnieszka Piwkowska
Podocytes and their foot processes form an important cellular layer of the glomerular barrier involved in the regulation of glomerular permeability. Disturbing the function of podocytes plays a central role in the development of proteinuria in diabetic nephropathy. Retraction of the podocyte foot processes that form slit diaphragms is a common feature of proteinuria; although, the correlation between these events in not well understood. Notably, it is unclear whether podocyte foot processes are able to regulate slit diaphragm permeability and glomerular ultrafiltration...
April 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27650398/high-intensity-interval-training-prevents-oxidant-mediated-diaphragm-muscle-weakness-in-hypertensive-mice
#10
T Scott Bowen, Sophia Eisenkolb, Juliane Drobner, Tina Fischer, Sarah Werner, Axel Linke, Norman Mangner, Gerhard Schuler, Volker Adams
Hypertension is a key risk factor for heart failure, with the latter characterized by diaphragm muscle weakness that is mediated in part by increased oxidative stress. In the present study, we used a deoxycorticosterone acetate (DOCA)-salt mouse model to determine whether hypertension could independently induce diaphragm dysfunction and further investigated the effects of high-intensity interval training (HIIT). Sham-treated (n = 11), DOCA-salt-treated (n = 11), and DOCA-salt+HIIT-treated (n = 15) mice were studied over 4 wk...
January 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27609832/skeletal-muscle-alterations-are-exacerbated-in-heart-failure-with-reduced-compared-with-preserved-ejection-fraction-mediated-by-circulating-cytokines
#11
Martin Seiler, T Scott Bowen, Natale Rolim, Maja-Theresa Dieterlen, Sarah Werner, Tomoya Hoshi, Tina Fischer, Norman Mangner, Axel Linke, Gerhard Schuler, Martin Halle, Ulrik Wisloff, Volker Adams
BACKGROUND: A greater understanding of the different underlying mechanisms between patients with heart failure with reduced (HFrEF) and with preserved (HFpEF) ejection fraction is urgently needed to better direct future treatment. However, although skeletal muscle impairments, potentially mediated by inflammatory cytokines, are common in both HFrEF and HFpEF, the underlying cellular and molecular alterations that exist between groups are yet to be systematically evaluated. The present study, therefore, used established animal models to compare whether alterations in skeletal muscle (limb and respiratory) were different between HFrEF and HFpEF, while further characterizing inflammatory cytokines...
September 2016: Circulation. Heart Failure
https://www.readbyqxmd.com/read/27595775/the-diaphragm-is-better-protected-from-oxidative-stress-than-hindlimb-skeletal-muscle-during-clp-induced-sepsis
#12
Hélène Talarmin, Frédéric Derbré, Luz Lefeuvre-Orfila, Karelle Léon, Mickaël Droguet, Jean-Pierre Pennec, Marie-Agnès Giroux-Metgès
OBJECTIVES: The aim of this study was to determine whether non-lethal sepsis induced by cecal ligation and puncture (CLP) modulates oxidative damage and enzymatic antioxidant defenses in diaphragm and hindlimb skeletal muscles (soleus and Extensor Digitorus Longus (EDL)). METHODS: Female Wistar rats were divided into four experimental groups: (1) control animals, (2) animals sacrificed 2 hours or (3) 7 days after CLP, and (4) sham-operated animals. At the end of the experimental procedure, EDL, soleus, and diaphragm muscles were harvested and 4-hydroxynonenal (HNE)-protein adducts and protein carbonyl contents were examined in relation to superoxide dismutase and catalase expression and activities...
September 6, 2016: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/27558126/influence-of-weaning-methods-on-the-diaphragm-after-mechanical-ventilation-in-a-rat-model
#13
Christian S Bruells, Thomas Breuer, Karen Maes, Ingmar Bergs, Christian Bleilevens, Gernot Marx, Joachim Weis, Ghislaine Gayan-Ramirez, Rolf Rossaint
BACKGROUND: Mechanical ventilation (MV) is associated with diaphragm weakness, a phenomenon termed ventilator-induced diaphragmatic dysfunction. Weaning should balance diaphragmatic loading as well as prevention of overload after MV. The weaning methods pressure support ventilation (PSV) and spontaneous breathing trials (SBT) lead to gradual or intermittent reloading of a weak diaphragm, respectively. This study investigated which weaning method allows more efficient restoration of diaphragm homeostasis...
2016: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/27553431/diaphragm-dysfunction-in-mechanically-ventilated-patients
#14
Irene Dot, Purificación Pérez-Teran, Manuel-Andrés Samper, Joan-Ramon Masclans
Muscle involvement is found in most critical patients admitted to the intensive care unit (ICU). Diaphragmatic muscle alteration, initially included in this category, has been differentiated in recent years, and a specific type of muscular dysfunction has been shown to occur in patients undergoing mechanical ventilation. We found this muscle dysfunction to appear in this subgroup of patients shortly after the start of mechanical ventilation, observing it to be mainly associated with certain control modes, and also with sepsis and/or multi-organ failure...
August 20, 2016: Archivos de Bronconeumología
https://www.readbyqxmd.com/read/27549759/phenotypic-and-metabolic-features-of-mouse-diaphragm-and-gastrocnemius-muscles-in-chronic-lung-carcinogenesis-influence-of-underlying-emphysema
#15
Anna Salazar-Degracia, David Blanco, Mònica Vilà-Ubach, Gabriel de Biurrun, Carlos Ortiz de Solórzano, Luis M Montuenga, Esther Barreiro
BACKGROUND: Muscle wasting negatively impacts the progress of chronic diseases such as lung cancer (LC) and emphysema, which are in turn interrelated. OBJECTIVES: We hypothesized that muscle atrophy and body weight loss may develop in an experimental mouse model of lung carcinogenesis, that the profile of alterations in muscle fiber phenotype (fiber type composition and morphometry, muscle structural alterations, and nuclear apoptosis), and in muscle metabolism are similar in both respiratory and limb muscles of the tumor-bearing mice, and that the presence of underlying emphysema may influence those events...
2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27515219/renin-angiotensin-system-in-ventilator-induced-diaphragmatic-dysfunction-potential-protective-role-of-angiotensin-1-7
#16
Anna Sigurta', Vanessa Zambelli, Giacomo Bellani
Ventilator-induced diaphragmatic dysfunction is a feared complication of mechanical ventilation that adversely affects the outcome of intensive care patients. Human and animal studies demonstrate atrophy and ultrastructural alteration of diaphragmatic muscular fibers attributable to increased oxidative stress, depression of the anabolic pathway regulated by Insulin-like growing factor 1 and increased proteolysis. The renin-angiotensin system, through its main peptide Angiotensin II, plays a major role in skeletal muscle diseases, mainly increasing oxidative stress and inducing insulin resistance, atrophy and fibrosis...
September 2016: Medical Hypotheses
https://www.readbyqxmd.com/read/27457930/leaky-ryanodine-receptors-contribute-to-diaphragmatic-weakness-during-mechanical-ventilation
#17
Stefan Matecki, Haikel Dridi, Boris Jung, Nathalie Saint, Steven R Reiken, Valérie Scheuermann, Ségolène Mrozek, Gaetano Santulli, Alisa Umanskaya, Basil J Petrof, Samir Jaber, Andrew R Marks, Alain Lacampagne
Ventilator-induced diaphragmatic dysfunction (VIDD) refers to the diaphragm muscle weakness that occurs following prolonged controlled mechanical ventilation (MV). The presence of VIDD impedes recovery from respiratory failure. However, the pathophysiological mechanisms accounting for VIDD are still not fully understood. Here, we show in human subjects and a mouse model of VIDD that MV is associated with rapid remodeling of the sarcoplasmic reticulum (SR) Ca(2+) release channel/ryanodine receptor (RyR1) in the diaphragm...
August 9, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27394427/the-high-correlation-between-counts-and-area-fractions-of-lipofuscin-granules-a-biomarker-of-oxidative-stress-in-muscular-dystrophies
#18
Yoshiko Nakae, Peter J Stoward
Images of cryostat unstained sections of two skeletal muscles, diaphragm and extensor digitorum longus (EDL), from wild-type normal and dystrophic mdx mice were captured with a fluorescence microscope, binarised and analysed by an automated procedure using ImageJ free software. The numbers, Feret diameters and areas of autofluorescent lipofuscin (LF)-like granules in the sections were determined from the binary images. The mean numbers of counted LF granules per mm(3) muscle tissue correlated highly (r ≥ 0...
November 2016: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/27393154/mtorc2-signaling-regulates-nox4-induced-podocyte-depletion-in-diabetes
#19
Stephanie Eid, Suzan Boutary, Kawthar Braysh, Ramzi Sabra, Charbel Massaad, Ahmed Hamdy, Awad Rashed, Sarah Moodad, Karen Block, Yves Gorin, Hanna E Abboud, Assaad Antoine Eid
AIM: Podocyte apoptosis is a critical mechanism for excessive loss of urinary albumin that eventuates in kidney fibrosis. Oxidative stress plays a critical role in hyperglycemia-induced glomerular injury. We explored the hypothesis that mTORC2 mediates podocyte injury in diabetes. RESULTS: High glucose (HG) induces podocyte injury reflected by alteration in the slit diaphragm protein podocin and podocyte depletion/apoptosis. This was paralleled by activation of the Rictor/mTORC2/Akt pathway...
July 8, 2016: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27388219/nmda-receptors-as-potential-therapeutic-targets-in-diabetic-nephropathy-increased-renal-nmda-receptor-subunit-expression-in-akita-mice-and-reduced-nephropathy-following-sustained-treatment-with-memantine-or-mk-801
#20
Hila Roshanravan, Eun Young Kim, Stuart E Dryer
N-methyl-d-aspartate (NMDA) receptors are expressed throughout the kidney, and the abundance of these receptors and some of their endogenous agonists are increased in diabetes. Moreover, sustained activation of podocyte NMDA receptors induces Ca(2+) influx, oxidative stress, loss of slit diaphragm proteins, and apoptosis. We observed that NMDA receptor subunits and their transcripts are increased in podocytes and mesangial cells cultured in elevated glucose compared with controls. A similar increase in NMDA subunits, especially NR1, NR2A, and NR2C, was observed in glomeruli and tubules of Akita mice...
October 2016: Diabetes
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