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MAPK-activated protein kinase 2-deficiency causes hyperacute tumor necrosis factor-induced inflammatory shock. mapk活化的蛋白激酶2缺乏引起超急性肿瘤坏死因子诱导的炎症性休克。
BMC Physiology Pub Date : 2014-09-04 DOI: 10.1186/s12899-014-0005-1
Benjamin Vandendriessche, An Goethals, Alba Simats, Evelien Van Hamme, Peter Brouckaert, Anje Cauwels
{"title":"MAPK-activated protein kinase 2-deficiency causes hyperacute tumor necrosis factor-induced inflammatory shock.","authors":"Benjamin Vandendriessche,&nbsp;An Goethals,&nbsp;Alba Simats,&nbsp;Evelien Van Hamme,&nbsp;Peter Brouckaert,&nbsp;Anje Cauwels","doi":"10.1186/s12899-014-0005-1","DOIUrl":"https://doi.org/10.1186/s12899-014-0005-1","url":null,"abstract":"<p><strong>Background: </strong>MAPK-activated protein kinase 2 (MK2) plays a pivotal role in the cell response to (inflammatory) stress. Among others, MK2 is known to be involved in the regulation of cytokine mRNA metabolism and regulation of actin cytoskeleton dynamics. Previously, MK2-deficient mice were shown to be highly resistant to LPS/d-Galactosamine-induced hepatitis. Additionally, research in various disease models has indicated the kinase as an interesting inhibitory drug target for various acute or chronic inflammatory diseases.</p><p><strong>Results: </strong>We show that in striking contrast to the known resistance of MK2-deficient mice to a challenge with LPS/D-Gal, a low dose of tumor necrosis factor (TNF) causes hyperacute mortality via an oxidative stress driven mechanism. We identified in vivo defects in the stress fiber response in endothelial cells, which could have resulted in reduced resistance of the endothelial barrier to deal with exposure to oxidative stress. In addition, MK2-deficient mice were found to be more sensitive to cecal ligation and puncture-induced sepsis.</p><p><strong>Conclusions: </strong>The capacity of the endothelial barrier to deal with inflammatory and oxidative stress is imperative to allow a regulated immune response and maintain endothelial barrier integrity. Our results indicate that, considering the central role of TNF in pro-inflammatory signaling, therapeutic strategies examining pharmacological inhibition of MK2 should take potentially dangerous side effects at the level of endothelial barrier integrity into account.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":"14 ","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2014-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12899-014-0005-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32637748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 11
Impact of maternal dietary fat supplementation during gestation upon skeletal muscle in neonatal pigs. 妊娠期饲粮中添加脂肪对新生猪骨骼肌的影响。
BMC Physiology Pub Date : 2014-08-27 DOI: 10.1186/s12899-014-0006-0
Hernan P Fainberg, Kayleigh L Almond, Dongfang Li, Cyril Rauch, Paul Bikker, Michael E Symonds, Alison Mostyn
{"title":"Impact of maternal dietary fat supplementation during gestation upon skeletal muscle in neonatal pigs.","authors":"Hernan P Fainberg,&nbsp;Kayleigh L Almond,&nbsp;Dongfang Li,&nbsp;Cyril Rauch,&nbsp;Paul Bikker,&nbsp;Michael E Symonds,&nbsp;Alison Mostyn","doi":"10.1186/s12899-014-0006-0","DOIUrl":"https://doi.org/10.1186/s12899-014-0006-0","url":null,"abstract":"<p><strong>Background: </strong>Maternal diet during pregnancy can modulate skeletal muscle development of the offspring. Previous studies in pigs have indicated that a fat supplemented diet during pregnancy can improve piglet outcome, however, this is in contrast to human studies suggesting adverse effects of saturated fats during pregnancy. This study aimed to investigate the impact of a fat supplemented (palm oil) \"high fat\" diet on skeletal muscle development in a porcine model. Histological and metabolic features of the biceps femoris muscle obtained from 7-day-old piglets born to sows assigned to either a commercial (C, n = 7) or to an isocaloric fat supplementation diet (\"high fat\" HF, n = 7) during pregnancy were assessed.</p><p><strong>Results: </strong>Offspring exposed to a maternal HF diet demonstrated enhanced muscular development, reflected by an increase in fractional growth rate, rise in myofibre cross-sectional area, increased storage of glycogen and reduction in lipid staining of myofibres. Although both groups had similar intramuscular protein and triglyceride concentrations, the offspring born to HF mothers had a higher proportion of arachidonic acid (C20:4n6) and a reduction in α-linolenic acid (C18:3n3) compared to C group offspring. The HF group muscle also exhibited a higher ratio of C20:3n6 to C20:4n6 and total n-6 to n-3 in conjunction with up-regulation of genes associated with free fatty acid uptake and biogenesis.</p><p><strong>Conclusion: </strong>In conclusion, a HF gestational diet accelerates the maturation of offspring biceps femoris muscle, reflected in increased glycolytic metabolism and fibre cross sectional area, differences accompanied with a potential resetting of myofibre nutrient uptake.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":"14 ","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2014-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12899-014-0006-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32640247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 12
Sympathoactivation and rho-kinase-dependent baroreflex function in experimental renovascular hypertension with reduced kidney mass. 实验性肾血管性高血压伴肾块减少的交感神经激活和rho激酶依赖的压力反射功能。
BMC Physiology Pub Date : 2014-06-19 DOI: 10.1186/1472-6793-14-4
Rainer U Pliquett, Sebastian Benkhoff, Oliver Jung, Ralf P Brandes
{"title":"Sympathoactivation and rho-kinase-dependent baroreflex function in experimental renovascular hypertension with reduced kidney mass.","authors":"Rainer U Pliquett,&nbsp;Sebastian Benkhoff,&nbsp;Oliver Jung,&nbsp;Ralf P Brandes","doi":"10.1186/1472-6793-14-4","DOIUrl":"https://doi.org/10.1186/1472-6793-14-4","url":null,"abstract":"<p><strong>Background: </strong>Dysregulation of the autonomic nervous system is frequent in subjects with cardiovascular disease. The contribution of different forms of renovascular hypertension and the mechanisms contributing to autonomic dysfunction in hypertension are incompletely understood. Here, murine models of renovascular hypertension with preserved (2-kidneys-1 clip, 2K1C) and reduced (1-kidney-1 clip, 1K1C) kidney mass were studied with regard to autonomic nervous system regulation (sympathetic tone: power-spectral analysis of systolic blood pressure; parasympathetic tone: power-spectral analysis of heart rate) and baroreflex sensitivity of heart rate by spontaneous, concomitant changes of systolic blood pressure and pulse interval. Involvement of the renin-angiotensin system and the rho-kinase pathway were determined by application of inhibitors.</p><p><strong>Results: </strong>C57BL6N mice (6 to 11) with reduced kidney mass (1K1C) or with preserved kidney mass (2K1C) developed a similar degree of hypertension. In comparison to control mice, both models presented with a significantly increased sympathetic tone and lower baroreflex sensitivity of heart rate. However, only 2K1C animals had a lower parasympathetic tone, whereas urinary norepinephrine excretion was reduced in the 1K1C model. Rho kinase inhibition given to a subset of 1K1C and 2K1C animals improved baroreflex sensitivity of heart rate selectively in the 1K1C model. Rho kinase inhibition had no additional effects on autonomic nervous system in either model of renovascular hypertension and did not change the blood pressure. Blockade of AT1 receptors (in 2K1C animals) normalized the sympathetic tone, decreased resting heart rate, improved baroreflex sensitivity of heart rate and parasympathetic tone.</p><p><strong>Conclusions: </strong>Regardless of residual renal mass, blood pressure and sympathetic tone are increased, whereas baroreflex sensitivity is depressed in murine models of renovascular hypertension. Reduced norepinephrine excretion and/or degradation might contribute to sympathoactivation in renovascular hypertension with reduced renal mass (1K1C). Overall, the study helps to direct research to optimize medical therapy of hypertension.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":"14 ","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2014-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6793-14-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32438803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 10
Reductions in expression of growth regulating genes in skeletal muscle with age in wild type and myostatin null mice. 野生型和肌肉生长抑制素缺失小鼠骨骼肌中生长调节基因表达随年龄的减少。
BMC Physiology Pub Date : 2014-03-28 DOI: 10.1186/1472-6793-14-3
Jennifer C Jones, Kellie A Kroscher, Anna C Dilger
{"title":"Reductions in expression of growth regulating genes in skeletal muscle with age in wild type and myostatin null mice.","authors":"Jennifer C Jones,&nbsp;Kellie A Kroscher,&nbsp;Anna C Dilger","doi":"10.1186/1472-6793-14-3","DOIUrl":"https://doi.org/10.1186/1472-6793-14-3","url":null,"abstract":"<p><strong>Background: </strong>Genes that decline in expression with age and are thought to coordinate growth cessation have been identified in various organs, but their expression in skeletal muscle is unknown. Therefore, our objective was to determine expression of these genes (Ezh2, Gpc3, Mdk, Mest, Mycn, Peg3, and Plagl1) in skeletal muscle from birth to maturity. We hypothesized that expression of these genes would decline with age in skeletal muscle but differ between sexes and between wild type and myostatin null mice.</p><p><strong>Results: </strong>Female and male wild type and myostatin null mice (C57BL/6J background) were sacrificed by carbon dioxide asphyxiation followed by decapitation at d -7, 0, 21, 42, and 70 days of age. Whole bodies at d -7, all muscles from both hind limbs at d 0, and bicep femoris muscle from d 21, 42 and 70 were collected. Gene expression was determined by quantitative real-time PCR. In general, expression of these growth-regulating genes was reduced at d 21 compared with day 0 and d -7. Expression of Gpc3, Mest, and Peg3 was further reduced at d 42 and 70 compared with d 21, however the expression of Mycn increased from d 21 to d 42 and 70. Myostatin null mice, as expected, were heavier with increased biceps femoris weight at d 70. However, with respect to sex and genotype, there were few differences in expression. Expression of Ezh2 was increased at d 70 and expression of Mdk was increased at d 21 in myostatin null mice compared with wild type, but no other genotype effects were present. Expression of Mdk was increased in females compared to males at d 70, but no other sex effects were present.</p><p><strong>Conclusions: </strong>Overall, these data suggest the downregulation of these growth-regulating genes with age might play a role in the coordinated cessation of muscle growth similar to organ growth but likely have a limited role in the differences between sexes or genotypes.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":"14 ","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2014-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6793-14-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32216464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
Cardiac responses to elevated seawater temperature in Atlantic salmon. 大西洋鲑鱼对海水温度升高的心脏反应。
BMC Physiology Pub Date : 2014-03-01 DOI: 10.1186/1472-6793-14-2
Sven Martin Jørgensen, Vicente Castro, Aleksei Krasnov, Jacob Torgersen, Gerrit Timmerhaus, Ernst Morten Hevrøy, Tom Johnny Hansen, Sissel Susort, Olav Breck, Harald Takle
{"title":"Cardiac responses to elevated seawater temperature in Atlantic salmon.","authors":"Sven Martin Jørgensen,&nbsp;Vicente Castro,&nbsp;Aleksei Krasnov,&nbsp;Jacob Torgersen,&nbsp;Gerrit Timmerhaus,&nbsp;Ernst Morten Hevrøy,&nbsp;Tom Johnny Hansen,&nbsp;Sissel Susort,&nbsp;Olav Breck,&nbsp;Harald Takle","doi":"10.1186/1472-6793-14-2","DOIUrl":"https://doi.org/10.1186/1472-6793-14-2","url":null,"abstract":"<p><strong>Background: </strong>Atlantic salmon aquaculture operations in the Northern hemisphere experience large seasonal fluctuations in seawater temperature. With summer temperatures often peaking around 18-20°C there is growing concern about the effects on fish health and performance. Since the heart has a major role in the physiological plasticity and acclimation to different thermal conditions in fish, we wanted to investigate how three and eight weeks exposure of adult Atlantic salmon to 19°C, previously shown to significantly reduce growth performance, affected expression of relevant genes and proteins in cardiac tissues under experimental conditions.</p><p><strong>Results: </strong>Transcriptional responses in cardiac tissues after three and eight weeks exposure to 19°C (compared to thermal preference, 14°C) were analyzed with cDNA microarrays and validated by expression analysis of selected genes and proteins using real-time qPCR and immunofluorescence microscopy. Up-regulation of heat shock proteins and cell signaling genes may indicate involvement of the unfolded protein response in long-term acclimation to elevated temperature. Increased immunofluorescence staining of inducible nitric oxide synthase in spongy and compact myocardium as well as increased staining of vascular endothelial growth factor in epicardium could reflect induced vascularization and vasodilation, possibly related to increased oxygen demand. Increased staining of collagen I in the compact myocardium of 19°C fish may be indicative of a remodeling of connective tissue with long-term warm acclimation. Finally, higher abundance of transcripts for genes involved in innate cellular immunity and lower abundance of transcripts for humoral immune components implied altered immune competence in response to elevated temperature.</p><p><strong>Conclusions: </strong>Long-term exposure of Atlantic salmon to 19°C resulted in cardiac gene and protein expression changes indicating that the unfolded protein response, vascularization, remodeling of connective tissue and altered innate immune responses were part of the cardiac acclimation or response to elevated temperature.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":"14 ","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2014-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6793-14-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32162950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 33
Kcnq1-5 (Kv7.1-5) potassium channel expression in the adult zebrafish. Kcnq1-5 (Kv7.1-5)钾通道在成年斑马鱼中的表达。
BMC Physiology Pub Date : 2014-02-20 DOI: 10.1186/1472-6793-14-1
Calvin Wu, Kanishk Sharma, Kyle Laster, Mohamed Hersi, Christina Torres, Thomas J Lukas, Ernest J Moore
{"title":"Kcnq1-5 (Kv7.1-5) potassium channel expression in the adult zebrafish.","authors":"Calvin Wu,&nbsp;Kanishk Sharma,&nbsp;Kyle Laster,&nbsp;Mohamed Hersi,&nbsp;Christina Torres,&nbsp;Thomas J Lukas,&nbsp;Ernest J Moore","doi":"10.1186/1472-6793-14-1","DOIUrl":"https://doi.org/10.1186/1472-6793-14-1","url":null,"abstract":"<p><strong>Background: </strong>KCNQx genes encode slowly activating-inactivating K+ channels, are linked to physiological signal transduction pathways, and mutations in them underlie diseases such as long QT syndrome (KCNQ1), epilepsy in adults (KCNQ2/3), benign familial neonatal convulsions in children (KCNQ3), and hearing loss or tinnitus in humans (KCNQ4, but not KCNQ5). Identification of kcnqx potassium channel transcripts in zebrafish (Danio rerio) remains to be fully characterized although some genes have been mapped to the genome. Using zebrafish genome resources as the source of putative kcnq sequences, we investigated the expression of kcnq1-5 in heart, brain and ear tissues.</p><p><strong>Results: </strong>Overall expression of the kcnqx channel transcripts is similar to that found in mammals. We found that kcnq1 expression was highest in the heart, and also present in the ear and brain. kcnq2 was lowest in the heart, while kcnq3 was highly expressed in the brain, heart and ear. kcnq5 expression was highest in the ear. We analyzed zebrafish genomic clones containing putative kcnq4 sequences to identify transcripts and protein for this highly conserved member of the Kcnq channel family. The zebrafish appears to have two kcnq4 genes that produce distinct mRNA species in brain, ear, and heart tissues.</p><p><strong>Conclusions: </strong>We conclude that the zebrafish is an attractive model for the study of the KCNQ (Kv7) superfamily of genes, and are important to processes involved in neuronal excitability, cardiac anomalies, epileptic seizures, and hearing loss or tinnitus.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":"14 ","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2014-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6793-14-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32144152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 44
RETRACTION: The effect of marathon on mRNA expression of anti-apoptotic and pro-apoptotic proteins and sirtuins family in male recreational long-distance runners. 摘要:马拉松运动对男性休闲长跑运动员细胞抗凋亡、促凋亡蛋白及sirtuins家族mRNA表达的影响。
BMC Physiology Pub Date : 2014-01-10 DOI: 10.1186/1472-6793-13-13
{"title":"RETRACTION: The effect of marathon on mRNA expression of anti-apoptotic and pro-apoptotic proteins and sirtuins family in male recreational long-distance runners.","authors":"","doi":"10.1186/1472-6793-13-13","DOIUrl":"https://doi.org/10.1186/1472-6793-13-13","url":null,"abstract":"","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":"13 ","pages":"13"},"PeriodicalIF":0.0,"publicationDate":"2014-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6793-13-13","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32018697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inference of mechanical states of intestinal motor activity using hidden Markov models. 利用隐马尔可夫模型推断肠道运动活动的机械状态。
BMC Physiology Pub Date : 2013-12-11 DOI: 10.1186/1472-6793-13-14
Lukasz Wiklendt, Marcello Costa, Phil G Dinning
{"title":"Inference of mechanical states of intestinal motor activity using hidden Markov models.","authors":"Lukasz Wiklendt,&nbsp;Marcello Costa,&nbsp;Phil G Dinning","doi":"10.1186/1472-6793-13-14","DOIUrl":"https://doi.org/10.1186/1472-6793-13-14","url":null,"abstract":"<p><strong>Background: </strong>Contractions and relaxations of the muscle layers within the digestive tract alter the external diameter and the internal pressures. These changes in diameter and pressure move digesting food and waste products. Defining these complex relationships is a fundamental step for neurogastroenterologists to be able define normal and abnormal gut motility.</p><p><strong>Results: </strong>Utilising an in vitro technique that allows for the simultaneous recording of intraluminal pressure (manometry) and gut diameter (video) in an isolated section of rabbit colon, we developed a technique to help define the mechanical states of the muscle at any point in space and time during actual peristaltic movements. This was achieved by directly relating the changes in pressure to the changes in diameter along the length of the gut studied. For each individual measure of pressure or diameter, 3 dynamic state components were identified; increasing or decreasing changes or a stable period. Two additional static state components, fully contracted and fully distended, were defined for the diameter. Then qualitative mechanical states of the muscle activity were defined as combinations of these state components. A hidden Markov model was used to correlate adjacent-in-time samples, and the Viterbi algorithm was used to infer the most likely sequence of mechanical states based on the observed data. From this a spatiotemporal map of the mechanical states was produced, showing the regions of active contractions, active relaxations, or passive states along the length of the gut throughout the entire recording period.</p><p><strong>Conclusions: </strong>The identification of mechanical muscles states based on gut diameter and intraluminal pressure was possible by modelling muscle activation with a hidden Markov model.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":"13 ","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2013-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6793-13-14","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31947748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 6
The endotoxin/toll-like receptor-4 axis mediates gut microvascular dysfunction associated with post-prandial lipidemia. 内毒素/toll样受体-4轴介导与餐后血脂相关的肠道微血管功能障碍。
BMC Physiology Pub Date : 2013-11-12 DOI: 10.1186/1472-6793-13-12
Ping Yi, Jia Pang, Jonathan Steven Alexander, Chantal Rivera
{"title":"The endotoxin/toll-like receptor-4 axis mediates gut microvascular dysfunction associated with post-prandial lipidemia.","authors":"Ping Yi,&nbsp;Jia Pang,&nbsp;Jonathan Steven Alexander,&nbsp;Chantal Rivera","doi":"10.1186/1472-6793-13-12","DOIUrl":"https://doi.org/10.1186/1472-6793-13-12","url":null,"abstract":"<p><strong>Background: </strong>Postprandial lipidemia is important in the development of coronary artery disease (CAD). Consumption of a meal high in monounsaturated fat was correlated with acute impairment of endothelial function. However, the mechanisms underlying impaired endothelial function in the postprandial state have not yet been elucidated. The effects of polyunsaturated fat (corn oil) and monounsaturated fat (olive oil) on vascular dysfunction in intestinal postcapillary venules and arterioles were examined in wild-type (WT) mice, mice genetically deficient in TLR4 (TLR4-/-) and mice pre-treated with antibiotics by intravital microscopy which was performed 1.0, 1.5, 2.0, 2.5 hours after oil administration. After intravital microscopy, samples of jejunum were therefore collected to test TLR4, pNF-kB p65 and SIRT1 protein expression by western blotting.</p><p><strong>Results: </strong>Our findings showed that feeding mono-unsaturated olive oil or polyunsaturated corn oil promoted leukocyte and platelet trafficking in the gut microvasculature, and impaired endothelium-dependent arteriolar vasodilator responses during postprandial lipidemia. The expression of TLR4, pNF-kB p65 was significantly increased in mice gavaged with olive oil at 2 h and was significantly reduced in mice gavaged for 7 days with antibiotics and in TLR4 knockout (TLR4-/-) mice. At the same time, SIRT1 protein expression is diminished by feeding olive oil for 2 h, a phenomenon that is attenuated in mice pre-treated with antibiotics and in TLR4-/- mice. Corn oil treated mice exhibited a pattern of response similar to olive oil.</p><p><strong>Conclusions: </strong>Dietary oils may be negative regulators of SIRT1 which activate the innate immune response through the endotoxin/TLR4 axis. Our findings establish a link between innate immunity (i.e. the endotoxin/TLR4 axis) and epigenetic controls mediated by SIRT1 in the genesis of diet associated vascular stress.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":"13 ","pages":"12"},"PeriodicalIF":0.0,"publicationDate":"2013-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6793-13-12","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31856347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
Overtraining is associated with DNA damage in blood and skeletal muscle cells of Swiss mice. 过度训练与瑞士小鼠血液和骨骼肌细胞中的 DNA 损伤有关。
BMC Physiology Pub Date : 2013-10-08 DOI: 10.1186/1472-6793-13-11
Bruno Cesar Pereira, José Rodrigo Pauli, Lusânia Maria Greggi Antunes, Ellen Cristini de Freitas, Mara Ribeiro de Almeida, Vinícius de Paula Venâncio, Eduardo Rochete Ropelle, Claudio Teodoro de Souza, Dennys Esper Cintra, Marcelo Papoti, Adelino Sanchez Ramos da Silva
{"title":"Overtraining is associated with DNA damage in blood and skeletal muscle cells of Swiss mice.","authors":"Bruno Cesar Pereira, José Rodrigo Pauli, Lusânia Maria Greggi Antunes, Ellen Cristini de Freitas, Mara Ribeiro de Almeida, Vinícius de Paula Venâncio, Eduardo Rochete Ropelle, Claudio Teodoro de Souza, Dennys Esper Cintra, Marcelo Papoti, Adelino Sanchez Ramos da Silva","doi":"10.1186/1472-6793-13-11","DOIUrl":"10.1186/1472-6793-13-11","url":null,"abstract":"<p><strong>Background: </strong>The alkaline version of the single-cell gel (comet) assay is a useful method for quantifying DNA damage. Although some studies on chronic and acute effects of exercise on DNA damage measured by the comet assay have been performed, it is unknown if an aerobic training protocol with intensity, volume, and load clearly defined will improve performance without leading to peripheral blood cell DNA damage. In addition, the effects of overtraining on DNA damage are unknown. Therefore, this study aimed to examine the effects of aerobic training and overtraining on DNA damage in peripheral blood and skeletal muscle cells in Swiss mice. To examine possible changes in these parameters with oxidative stress, we measured reduced glutathione (GSH) levels in total blood, and GSH levels and lipid peroxidation in muscle samples.</p><p><strong>Results: </strong>Performance evaluations (i.e., incremental load and exhaustive tests) showed significant intra and inter-group differences. The overtrained (OTR) group showed a significant increase in the percentage of DNA in the tail compared with the control (C) and trained (TR) groups. GSH levels were significantly lower in the OTR group than in the C and TR groups. The OTR group had significantly higher lipid peroxidation levels compared with the C and TR groups.</p><p><strong>Conclusions: </strong>Aerobic and anaerobic performance parameters can be improved in training at maximal lactate steady state during 8 weeks without leading to DNA damage in peripheral blood and skeletal muscle cells or to oxidative stress in skeletal muscle cells. However, overtraining induced by downhill running training sessions is associated with DNA damage in peripheral blood and skeletal muscle cells, and with oxidative stress in skeletal muscle cells and total blood.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":"13 ","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2013-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3852772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31784665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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