bluuebunny/crossref_metadata_2025_split huggingface dataset:
REDUCTION OF FATIGUE IN SKELETAL MUSCLE BY DIAZOXIDE: POSSIBLE PARTICIPATION OF MITOKATP.
Authors: Sánchez-Duarte Elizabeth , Montoya-Pérez Rocío , Trujillo-Trujillo Xóchitl , Vázquez-Rivera Dolores , Cortés-Rojo Christian , Meza-Carmen Victor , Saavedra-Molina Alfredo 
Published: June 2021

The decrease in the ATP has an important role in the development of muscle fatigue and any event related to alteration of production of energy, this determine the tendency of muscle fatigue (Allen et al. 2008). KATP channels have been described in the inner mitochondrial membrane (mitoKATP) (Inoue et al. 1991). Garcia et al. (2009) showed that mitoKATP plays an important role in protecting the muscle during fatigue. The intention of this study was to determine the possible participation of mitoKATP channels during fatigue exploring the effect of Diazoxide (a selective activator) and selective inhibitor 5‐HD, in tension of slow skeletal muscle of chicken in a in vitro model of fatigue.Anterior Latissimus Dorsi (ALD) muscle of Arbor acres variety chicken was used. The muscle was mounted on an experimental recording chamber by mecanoelectric transducer (Grass FT03), which through an amplifier and a analog‐digital interface (Digidata 1322A) allowed to acquire the muscle tension generated by a computer (Pentium 4) and a “software” of data acquisition (pCLAMP 9.2). The muscle was stimulated until the force decreased by 70‰ repetitive electrical stimulation, then applied Diazoxide for 6 min to observe its effect (10, 30 and 100 μM, and 500 μM of 5‐HD.In a Diazoxide dose‐response curve, effect of 30 μM increased postfatige tension (40.67±8‰), combination 5‐HD with Diazoxide had no significant effect in fatigue. The results shows a protective effect of muscle by Diazoxide, however the lack of effect of 5‐HD may be due an unspecific interaction with channels of skeletal muscle.
Interleukin‐6/JAK/STAT3‐induced satellite cell proliferation is regulated through induction of Cyclin D1
Authors: Kurosaka Mitsutoshi , Machida Shuichi 
Published: June 2021

OBJECTIVETo determine the signaling mechanisms by which Interleukin‐6 (IL‐6) induces proliferative potential of satellite cells in culture.METHODSSatellite cells were isolated from 30 male F344 rats (average 11 weeks). Recombinant human IL‐6 at a concentration 1 or 10 ng/ml was added to the culture medium. Immunocytochemical analysis was performed to quantify phosphorylated STAT3 (pSTAT3)+/MyoD+cells and Cyclin D1+/MyoD+ cells. In addition, co‐localization of SOCS3and myogenin were detected by immunocytochemical staining. Cyclin D1 and SOCS3 mRNA was measured using RT‐PCR.ResultsWe previously confirmed that 1 ng/ml rhIL‐6 at concentration induces satellite cell proliferation. In the present experiments, the numbers of pSTAT3+/MyoD+cells and Cyclin D1+/MyoD+ cells and Cyclin D1 mRNA were was significantly higher following treatment with 1 ng/ml rhIL‐6 compared with control media (p < 0.05). The number of Cyclin D1+/MyoD+ cells also increased following treatment with 10 ng/ml rhIL‐6, which contrasts with our previous findings that this dose of IL‐6 inhibited satellite cell proliferation. In the present study, 10 ng/ml rhIL‐6 induced greater SOCS3 mRNA expression compared with 1 ng/ml and control media, and also increased the number of cells that co‐express SOCS3and myogenin.CONCLUSIONIL‐6 induces a dose‐dependent increase in proliferative potential of satellite cells through activation of JAK/STAT3/Cyclin D1 pathway.This work was supported by KAKENHI (22700659).
Studies of mitochondrial and non‐mitochondrial sources implicate NADPH oxidase(s) in the increased skeletal muscle superoxide generation that occurs during contractile activity
Authors: Sakellariou Giorgos K , Vasilaki Aphrodite , Palomero Jesus , Kayani Anna , Zibrik Lea , McArdle Anne , Jackson Malcolm J 
Published: June 2021

Superoxide generated by skeletal muscle acts to modulate force generation and contraction‐induced changes in gene expression. This study identified the sub‐cellular sites of muscle fibre superoxide generation. Single isolated mature fibres from mouse flexor digitorum brevis loaded with superoxide‐sensitive fluorescent probes, specific inhibitors of potential pathways and immunolocalisation techniques were used. Comparison of voltage dependent anion channel or Bax channel inhibitors following contractile activity or treatment with the mitochondrial compex III inhibitor, antimycin A, indicated that superoxide could exit mitochondria via these channels, but they did not contribute to contraction‐induced increases in cytosolic superoxide. NADPH oxidase inhibitors decreased superoxide at rest and following contractions compared with controls. Protein and mRNA expression of NADPH oxidase subunits were demonstrated in fibres. At rest, NOX2, NOX4 and p22phox subunits localized to the sarcolemma and transverse tubules and the regulatory subunits p40phox and p67phox localized to the cytoplasm. Following contractions, p40phox was observed to translocate from the fibre cytosol to the sarcolemma. NADPH oxidase is a major contributor to cytosolic superoxide in muscle and its activation by contractions involves translocation of p40phox from the cytosol to the sarcolemma.Funded by NIA (AG‐20591)
Prolactin's role during acute and chronic heat stress in growing pigs
Authors: Sanz-Fernandez Maria Victoria , Pearce S. C. , Upah N. C. , Long L. R. , Nayeri A. , Sucu E. , Gabler N. K. , Patience J. F. , Hsu W. H. , Rhoads R. P. , Baumgard L. H. 
Published: June 2021

Heat stress (HS) increases circulating prolactin (PRL) in a variety of animal models (reasons remain unknown), but whether or not HS elevates PRL in growing pigs is ill‐defined. Crossbred gilts (77±2 kg) were housed in individual pens and allocated to treatments: 1) HS conditions (36°C; 50% humidity) and ad libitum feeding (n=13) or 2) thermo‐neutral (TN) conditions (19°C; 61% humidity) and pair‐feeding (n=16) to eliminate the confounding effects of dissimilar feed intake. Pigs were sacrificed at d1 or 7 of environmental exposure. Rectal temperatures (Tr) and respiratory rates (RR) were obtained 4X daily and blood and intestinal tissues harvested at death. HS pigs had increased Tr (P<0.01; 40.1 vs. 38.4°C), RR (P<0.01; 111 vs. 36 bpm) and reduced feed intake (P<0.05; 57%). By design, TN pigs’ intake mirrored the HS pattern. PRL was higher (P<0.05) in HS pigs (0.97 vs. 0.64 ng/ml). In acute HS (24 h), PRL was negatively correlated with feed intake (r = −0.71; P<0.05), ileal transepithelial resistance (TER; r = −0.85; P<0.01) and tended to be negatively correlated with colonic TER (r = −0.69; P=0.06). In chronic HS (d7), PRL tended to be only inversely correlated with glucose (r = −0.81; P<0.10). In TN pigs, PRL was not correlated with any of the measured variables. Together, PRL appears to participate in both the acute HS response and the acclimation to chronic environmental hyperthermia.Heat stress, prolactinUSDA/AFRI
Improved temperature regulation following heat acclimation in well‐healed skin graft subjects exercising in the heat
Authors: Pearson James , Ganio Matt S , AI Lucas Rebekah , Crandall Craig G 
Published: June 2021

Burn victims with grafted skin have impaired heat dissipation. The effect of heat acclimation on temperature regulation in these individuals is unclear. This study tested the hypothesis that burn victims with significant amounts of grafted skin can heat acclimate. Two groups of burn survivors were evaluated: 20–40% body surface area (BSA) grafted (N=13) and 45–75% BSA grafted (N=7). Six non‐injured subjects served as controls. Subjects exercised for 45 min at 1 l/min O2 uptake in an environmental chamber (40°C, 30% RH) on days 1 and 7 of a heat acclimation regimen (45% VO2 max, 90 min per day; 40°C, 30% RH). Core body temperature (Tcore) was measured using an ingestible pill. On day 1 Tcore increased to a greater extent during exercise in the 45–75% BSA group (1.14 ± 0.34°C; P < 0.05) relative to 20–40% BSA (0.81 ± 0.23°C) and control groups (0.62 ± 0.32°C). On day 7, while the increase in Tcore during exercise for the 45–75% BSA group (0.78 ± 0.32°C) remained greater relative to controls (0.41 ± 0.24°C; P = 0.05), the increase in this grafted group was less than on day 1 (P = 0.03). However, the increase in Tcore in the 20–40% BSA group after heat acclimation on day 7 (0.68 ± 0.28) was not different to day 1 (P = 0.26). Temperature regulation is impaired in individuals with skin grafts covering 45–75%, but not 20–40% BSA. Importantly, temperature regulation can improve after heat acclimation in individuals with ≥45% BSA grafted.NIH GM068865
Regulation of rDNA transcription and ribosome biogenesis at the onset of skeletal muscle hypertrophy
Authors: von Walden Ferdinand , Farrants Ann-Kristin Östlund , Nader Gustavo A. 
Published: June 2021

We investigated the regulation of ribosomal (r)DNA gene transcription and ribosome production at the onset of skeletal muscle hypertrophy. Mice were subjected to functional overload of the plantaris muscle by bilateral removal of the synergist muscles. Mechanical loading resulted in muscle hypertrophy with an increase in rRNA content. rDNA transcription as determined by 45S pre‐RNA abundance paralleled the increase in rRNA content. Increased transcription and protein expression of c‐Myc and its downstream POL I regulon (POL1RB, TIF‐1A, PAF53, TTF1 & TAF1C) was consistent with the increase in rRNA. Other factors involved in rDNA transcription (UBF) and chromatin remodeling (WSTF) were induced by mechanical loading in a similar fashion. Chromatin‐IP revealed that these factors, together with histone H3 lysine 9 acetylation abundance relative to H3 were also enriched at the rDNA promoter. Our results demonstrate that mechanical loading induces ribosome production via epigenetic and transcriptional mechanisms at the rDNA promoter.Supported by the Swedish Research Council (VR) and the Swedish Nat Ctr for Sports Res (CIF)
Cumulative effects of successive bouts of maximal exercise on heart rate fluctuations
Authors: da Silva Soares Pedro Paulo , Calvão Angelo Mondaini , Sá Fernanda Lopes , Penna Thadeu Josino Pereira , de Menezes Márcio Argollo 
Published: June 2021

The aim of the present study was to investigate the cumulative effects of two bouts of maximal exercise on heart rate (HR) by spectral and detrended fluctuation analysis (DFA). Rowers (n=14, 11 males, 24±6 years old) performed two maximal (2k1 and 2k2) tests. HRV and DFA were calculated before (PRE1) and after 2k1 (POS1), four hours after POS1 (PRE2) and after 2k2 (POS2). The HF power was reduced from PRE1 (1527±1349 ms2) to POS1 (224±339 ms2) and from PRE2 (908±861 ms2) to POS2 (214±234 ms2, respectively, p<0.05) and in PRE2 was lower than PRE1 (p<0.05), with similar reductions in POS1 and POS2 (p>0.05). DFA in the time domain was used as a non‐linear method to quantify HR fluctuations detrended from its nonstationary background, giving a more precise measure of the fractality and long‐range correlations in the time series. DFA analysis is able to assess that HR fluctuations in POS2 were lower that POS1, moreover, the exponent α related to the fractal measure departs from a purely random one (α=0.5), evidencing long‐range correlations in HR variability, with slightly different exponents in PRE and POS groups. DFA showed that after 2k2 there was an additional reduction on HR fluctuations. These data suggest cumulative effects of exercise on HR dynamics and both methods give complementary information.Support: CNPq 481434/2008‐9 and FAPERJ E‐26/111.345/2011
Baroreflex responsiveness is attenuated in African Americans during steady‐state leg exercise
Authors: Holwerda Seth William , Samels Mitchel R , Keller David M 
Published: June 2021

Carotid baroreflex (CBR) responsiveness is impaired in African Americans (AA) compared to Caucasian Americans (CA) at rest. In addition, AA exhibit greater blood pressure responses to exercise compared to CA. We tested the hypothesis that CBR control of heart rate (HR) and mean arterial pressure (MAP) is reduced in AA compared to CA during steady‐state leg exercise. CBR control of HR and MAP was assessed in 11 AA and 11 CA subjects using 5s trials of neck pressure (NP, simulated hypotension: +45, +30, +15 Torr) and neck suction (NS, simulated hypertension: −20, −40, −60, −80 Torr). At rest, no racial differences were found in either the mean HR or the mean MAP responses to NP. While MAP responses to NS were similar between races at rest, the mean HR response to NS was attenuated in the AA group (−8.6±2.0bpm) compared to the CA group (−14.4±2.3bpm, p<0.05). During exercise (50% VO2peak), again no racial differences were found in either the mean HR or mean MAP responses to NP. However, the mean HR response to NS tended to be reduced in the AA group (−7.9±1.7bpm) compared to the CA group (− 11.0±3.1bpm, p=0.069) during exercise. Interestingly, the mean MAP response to NS was impaired in the AA group (− 6.5±0.8mmHg) compared to the CA group (−8.0±1.2mmHg, p<0.05) during exercise. These findings support inherent differences in CBR responsiveness in AA compared to CA during both rest and exercise.Support by NIH Grant R15HL096103
Angiotensin type 2 receptors (AT2R) over expression in the nucleus of the solitary tract (NTS) attenuate renovascular hypertension
Authors: Blanch Graziela Torres , Freiria-Oliveira Andre Henrique , Li Hongwei , Colombari Eduardo , Sumners Colin , Colombari Debora S. A. 
Published: June 2021

We have demonstrated that AT2R overexpression in the NTS decreases mean arterial pressure (MAP) in normotensive rats. The aim of the present study was to investigate the effects of AT2R overexpression in the NTS in two kidney 1 clip (2K1C) hypertensive rats. Holtzman male rats (150–180 g, n = 5–6/group) were implanted with telemetry transducers into the abdominal aorta followed by a silver clip implant in the left renal artery. Three weeks after the 2K1C surgery the NTS was microinjected (200 nl/site, 5 sites) with either adeno‐associated virus vector AAV2‐CBA‐AT2R (1×108 gc) or AAV2‐CBA‐eGFP (1×109 gc) for the over expression of AT2R or GFP, respectively. At that time period, rats were hypertensive (134±3 mmHg light period and 133±4 mmHg dark period) compared to baseline levels (light period: 101±3 mmHg; dark period: 110±5 mmHg). Three to 4 weeks after the NTS injections (6–7 weeks after 2K1C), at which time AT2R or GFP expression has reached maximal (and stable) levels, MAP reached values of 171±10 mmHg light period and 190±8 mmHg dark period in GFP rats. In the AT2R transduced 2K1C rats, the increase in MAP was significantly lower compared to GFP animals (151±6 mmHg light period; 153±7 mmHg dark period: p<0.05 vs. GFP group). These results suggest that overexpression of AT2R in the NTS impairs the development of renovascular hypertension.Supported by: PNPD/CAPES, CNPq and NIH Grant HL 076803
Aldosterone (Aldo) Interacts with PKA, MAPKs and PLC Pathway to Sensitize Angiotensin (ANG) II‐Induced Hypertension
Authors: Xue Baojian , Zhang Zhongming , Guo Fang , Johnson Alan Kim 
Published: June 2021

Previous studies using an Induction‐Delay‐Expression (I‐D‐E) experimental design have demonstrated that one‐week Aldo pre‐treatment can sensitize the brain to produce an enhanced hypertensive response to subsequent ANGII. The amplified pressor effects are associated with elevated mRNA expression of RAAS components in the lamina terminalis (LT). The present study was to determine the signaling mechanisms involved in the sensitizing effects of Aldo on the brain. During I Aldo (750 ng/h) or saline was delivered sc for 1 wk. The rats then rested for 1 wk (D). Then the tissues along LT were collected at the end of D for determining activation of PKA, MAPKs or PLC pathway.The week of Aldo treatment during I had no effect on BP during I and D. However, Aldo treatment during I induced a significant increase in phosphorylated cAMP response element‐binding protein (CREB, 1.5 fold), extracellular signal‐regulated kinase (ERK, 1.8 fold), or phospholipase C (PLC, 1.8 fold) in the LT. Moreover, Aldo infusion resulted in a significant increase in mRNA (1.5 fold) and protein (1.3 fold) expression of brain‐derived neurotrophic factor (BDNF) as compared with the saline treated rats. The results indicate that Aldo pre‐treatment may facilitate the development of ANG II‐induced hypertension by acting through a sensitization process involving PKA, MAPKs or PLC pathway.
Central cholinergic or angiotensinergic activation facilitates the pressor responses to glutamate injected into the RVLM
Authors: Gomide Joelma Maria Cardoso , Gasparini Silvia , De Luca Laurival Antonio , de Almeida Colombari Debora Simoes , De Paula Patricia Maria , Moreira Thiago Santos , Menani Jose Vanderlei 
Published: June 2021

In the present study, we investigated the cardiovascular responses produced by the injections of L‐glutamate into the rostroventrolateral medulla (RVLM) in conscious rats that previously received injections of carbachol (cholinergic agonist) or angiotensin II (ANG II) injected into the lateral ventricle (LV). Male Holtzman rats (280–320 g, n = 8, baseline mean arterial pressure = 117 ± 4 mmHg and baseline heart rate = 400 ± 17 bpm) with stainless steel guide‐cannulas implanted unilaterally in the LV and in the RVLM were used. The pressor response produced by the injections of L‐glutamate (5 nmol/100 nl) into the RVLM increased by pre‐treating the rats with carbachol (4 nmol/1 μl) or ANG II (50 ng/1 μl) icv (59 ± 3 and 68 ± 5 mmHg, respectively) compared to the control responses produced by L‐glutamate injected into the RVLM combined with saline icv (37 ± 3 mmHg). The pressor responses produced by the injection of carbachol or ANG II icv reached the maximum of 56 ± 3 and 44 ± 3 mmHg, respectively and they were reduced to 9 ± 2 and 6 ± 3 mmHg immediately before the injection of glutamate into the RVLM. Injection of carbachol or ANG II icv and L‐glutamate into the RVLM alone or combined produced no significant changes in the heart rate. These results suggest that central cholinergic or angiotensinergic activation facilitates the pressor response produced by glutamatergic activation of the RVLM.Financial support: FAPESP, CNPq.
Combining whole transcriptome expression with SILAC to investigate mTOR inhibition in cultured baboon fetal proximal tubule cells
Authors: Nakamura Michiyo , Cox Laura A , Glenn Jeremy P , Pardo Sammy , Habib Samy , Weintraub Susan P , Nijland Mark J 
Published: June 2021

Maternal nutrition during pregnancy influences fetal growth and postnatal health. The developing mammalian kidney is sensitive to alterations in its nutrient environment. The mammalian target of rapamycin (mTOR) signaling system acts as a nutrient sensor and key component of the cell stress response. We have combined transcriptomic and proteomic approaches to investigating inhibition of mTOR signaling in fetal baboon renal epithelial cells (PTC) in culture.Fetal PTCs were isolated at 0.5G from 5 fetal baboons. Equal numbers of cells were plated in 6 well plates containing standard culture medium or medium containing stable isotope‐labeled arginine and lysine (SILAC). Rapamycin (1 nM) or vehicle was added at 60% confluence and equal numbers of cells harvested 24h later. Transcriptome (Illumina BeadChip) and proteome (HPLC‐ESI‐MS/MS) analyses were performed. The union of transcripts for differentially expressed proteins detected by SILAC and differentially expressed genes detected by BeadChip was analyzed using ontology enrichment analysis.Ontologies down‐regulated by rapamycin include translation initiation, elongation and termination, protein complex disassembly, ribosome biosynthesis and assembly, Golgi vesicle budding and S‐adenosylmethionine biosynthesis and metabolism.We conclude that fetal baboon PTCs exhibit classic responsiveness to mTOR signaling inhibition.
Circadian expression of H,K‐ATPase type 2 contributes to the stability of plasma K+ levels
Authors: Crambert Gilles , Centeno Gabriel , Firsov Dmitri , Salhi Amel 
Published: June 2021

Maintenance by the kidney of stable plasma K+ values is crucial, as the latter control muscle and nerve activity. Inability to do so, induced hyper‐ or hypokalemia both related to heart dysfunctions, muscle weakness and neurological disorders.Since renal K+ excretion is regulated by the circadian clock we aimed to identify the ion transporters involved in this process.In control mice, the renal mRNA expression of the H,K‐ATPase type 2 (HKA2) is 25% higher during rest compared to the activity period. Conversely, under dietary K+ restriction, HKA2 expression is ~ 40% higher during the activity period. This reversal suggests that HKA2 contributes to the circadian regulation of K+ homeostasis. Compared to their wild‐type littermate (WT), HKA2‐ null mice on a normal diet have a 2‐fold higher K+ renal excretion during rest. Under K+ restriction, their urinary K+ loss is 40% higher during the activity period. This inability to excrete K+ “on time” is reflected in plasma K+ values, which vary by 12 % between activity and rest periods in HKA2‐null mice but remain stable in WT. Analysis of the circadian expression of HKA2 regulators suggests that Nrf2 but not progesterone contributes to its rhythmicity. Therefore, HKA2 acts to maintain the circadian rhythm of urinary K+ excretion and preserve stable plasma K+ values throughout the day.
Functional and structural regulation of urate handling by human SLC2A9 isoforms in the Xenopus laevis oocyte expression system
Authors: Cheeseman Chris I , Witkowska Kate , Long Toto 
Published: June 2021

Human GLUT9 (SLC2A9) is a high capacity urate transporter, backed by genome‐wide association scans. This gene's SNPs coincide with urate pathology1. The protein is predominant in liver and kidney, main organs in human urate homeostasis. Two splice variants of the carrier, SLC2A9a (A) and SLC2A9b (B), which differ in their residue composition in the N‐terminus, target differently to cell membranes of polarized epithelium2. Hydrophobic residues in this family of transporters were shown to play a role in hexose selectivity3.OBJECTIVESTo investigate differences in urate transport function and selectivity by SLC2A9 variants, for uptake and efflux modes.METHODhSLC2A9 isoforms and appropriate mutants were overexpressed in X. laevis oocytes. Radiolabelled urate uptake and efflux was measured under varied conditions.PKC agonist affects (A)‐ but not (B)‐mediated urate uptake and efflux. Kinetic experiments reveal that both affinity and capacity of the transporter are altered, without changes in funcional surface expression of the protein. Elevation of intracellular cAMP altered (B)‐ but not (A)‐mediated urate uptake under specific conditions. These observations suggest that urate reabsorption (A) and urate secretion (B) may be differentially regulated in polarized epithelia. Furthermore, hydrophobic residues around exofacial vestibule may act as hexose and urate selectivity determinants.