Expression of osmotic stress-related genes in tissues of normal and hyposmotic rats

2003 ◽  
Vol 285 (4) ◽  
pp. F688-F693 ◽  
Author(s):  
Zheng Zhang ◽  
Joan D. Ferraris ◽  
Heddwen L. Brooks ◽  
Ioana Brisc ◽  
Maurice B. Burg
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factor ◽  
Mrna Expression ◽  
Plasma Osmolality ◽  
Hsp 70 ◽  
Taurine Transporter ◽  
Osmolyte Accumulation ◽  
Organic Osmolyte ◽  
Stress Related Genes ◽  
Control Plasma

TonEBP is a transcription factor that, when activated by hypertonicity, increases transcription of genes, including those involved in organic osmolyte accumulation. Surprisingly, it is expressed in virtually all tissues, including many never normally exposed to hypertonicity. We measured TonEBP mRNA (real-time PCR) and protein (Western blot analysis) in tissues of control (plasma osmolality 294 ± 1 mosmol/kgH2O) and hyposmotic (dDAVP infusion plus water loading for 3 days, 241 ± 2 mosmol/kgH2O) rats to test whether the ubiquitous expression of TonEBP mRNA is osmotically regulated around the normal plasma osmolality. TonEBP protein is reduced by hyposmolality in thymus and liver, but not in brain, and is not detected in heart and skeletal muscle. TonEBP mRNA decreases in brain and liver but is unchanged in other tissues. There are no general changes in mRNA of TonEBP-mediated genes: aldose reductase (AR) does not change in any tissue, betaine transporter (BGT1) decreases only in liver, taurine transporter (TauT) only in brain and thymus, and inositol transporter (SMIT) only in skeletal muscle and liver. Heat shock protein (Hsp)70–1 and Hsp70–2 mRNA increase greatly in most tissues, which cannot be attributed to decreased TonEBP activity. The conclusions are as follows: 1) TonEBP protein or mRNA expression is reduced by hyposmolality in thymus, liver, and brain. 2) TonEBP protein and mRNA expression are differentially regulated in some tissues. 3) Although AR, SMIT, BGT1, and TauT are regulated by TonEBP in renal medullary cells, other sources of regulation may predominate in other tissues. 4) TonEBP abundance and activity are regulated by factors other than tonicity in some tissues.

scholarly journals Induction of autophagy through the activating transcription factor 4 (ATF4)-dependent amino acid response pathway in maternal skeletal muscle may function as the molecular memory in response to gestational protein restriction to alert offspring to maternal nutrition

2015 ◽  
Vol 114 (4) ◽  
pp. 519-532 ◽  
Author(s):  
Huan Wang ◽  
Gabriel J. Wilson ◽  
Dan Zhou ◽  
Stéphane Lezmi ◽  
Xiuwen Chen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factor ◽  
Amino Acid ◽  
Protein Expression ◽  
Mrna Expression ◽  
Protein Restriction ◽  
Activating Transcription Factor 4 ◽  
Activating Transcription Factor ◽  
Transcription Factor 4

The aim of the present study was to investigate the mechanistic basis of protein deficiency during pregnancy in mother that is transduced to offspring. To this end, timed-pregnant Sprague–Dawley rats were fed either a control (20 % of energy from protein) or low-protein (LP, 8 % of energy from protein) diet during gestation. Tissues were collected after delivery from rat dams, and skeletal muscle was collected at postnatal day 38 from the offspring. Quantitative RT-PCR and Western blot analyses were performed to determine mRNA and protein levels. Histological analysis was performed to evaluate myofibre size. LP dams gained significantly less weight during pregnancy, developed muscle atrophy, and had significantly lower circulating threonine and histidine levels than control dams. The mRNA expression of the well-known amino acid response (AAR) pathway-related target genes was increased only in the skeletal muscle of LP dams, as well as the protein expression levels of activating transcription factor 4 (ATF4) and phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α). The mRNA expression of autophagy-related genes was significantly increased in the skeletal muscle of LP dams. Moreover, the mRNA expression of genes involved in both AAR and autophagy pathways remained elevated and was memorised in the muscle of LP offspring that consumed a post-weaning control diet. Additionally, the LP diet increased an autophagy marker, microtubule-associated proteins 1A/1B light chain 3B (LC3B) protein expression in the skeletal muscle of rat dams, consistent with the initiation of autophagy. The LP diet further increased ATF4 binding at the predicted regions of AAR and autophagy pathway-related genes. Increased binding of ATF4 unveils the crucial role of ATF4 in the activation of autophagy in response to protein restriction. Our data suggest that molecular changes in maternal muscle are memorised in the offspring long after gestational protein restriction, reinforcing the role of maternal signalling in programming offspring health.

scholarly journals Effects of spaceflight on murine skeletal muscle gene expression

2009 ◽  
Vol 106 (2) ◽  
pp. 582-595 ◽  
Author(s):  
David L. Allen ◽  
Eric R. Bandstra ◽  
Brooke C. Harrison ◽  
Seiha Thorng ◽  
Louis S. Stodieck ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Transcription Factor ◽  
Mrna Expression ◽  
Muscle Growth ◽  
Insulin Response ◽  
Hindlimb Suspension ◽  
Regulatory Subunit ◽  
Fiber Types ◽  
Mrna Levels

Spaceflight results in a number of adaptations to skeletal muscle, including atrophy and shifts toward faster muscle fiber types. To identify changes in gene expression that may underlie these adaptations, we used both microarray expression analysis and real-time polymerase chain reaction to quantify shifts in mRNA levels in the gastrocnemius from mice flown on the 11-day, 19-h STS-108 shuttle flight and from normal gravity controls. Spaceflight data also were compared with the ground-based unloading model of hindlimb suspension, with one group of pure suspension and one of suspension followed by 3.5 h of reloading to mimic the time between landing and euthanization of the spaceflight mice. Analysis of microarray data revealed that 272 mRNAs were significantly altered by spaceflight, the majority of which displayed similar responses to hindlimb suspension, whereas reloading tended to counteract these responses. Several mRNAs altered by spaceflight were associated with muscle growth, including the phosphatidylinositol 3-kinase regulatory subunit p85α, insulin response substrate-1, the forkhead box O1 transcription factor, and MAFbx/atrogin1. Moreover, myostatin mRNA expression tended to increase, whereas mRNA levels of the myostatin inhibitor FSTL3 tended to decrease, in response to spaceflight. In addition, mRNA levels of the slow oxidative fiber-associated transcriptional coactivator peroxisome proliferator-associated receptor (PPAR)-γ coactivator-1α and the transcription factor PPAR-α were significantly decreased in spaceflight gastrocnemius. Finally, spaceflight resulted in a significant decrease in levels of the microRNA miR-206. Together these data demonstrate that spaceflight induces significant changes in mRNA expression of genes associated with muscle growth and fiber type.

PGC-1α mRNA expression is influenced by metabolic perturbation in exercising human skeletal muscle

2004 ◽  
Vol 96 (1) ◽  
pp. 189-194 ◽  
Author(s):  
Jessica Norrbom ◽  
Carl Johan Sundberg ◽  
Helene Ameln ◽  
William E. Kraus ◽  
Eva Jansson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Transcription Factor ◽  
Mrna Expression ◽  
Mitochondrial Biogenesis ◽  
Human Skeletal Muscle ◽  
Fiber Type ◽  
Mitochondrial Transcription ◽  
Mitochondrial Transcription Factor ◽  
Metabolic Perturbation

Endurance training leads to many adaptational changes in several tissues. In skeletal muscle, fatty acid usage is enhanced and mitochondrial content is increased. The exact molecular mechanisms regulating these functional and structural changes remain to be elucidated. Contractile activity-induced metabolic perturbation has repeatedly been shown to be important for the induction of mitochondrial biogenesis. Recent reports suggest that the peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α)/mitochondrial transcription factor A (Tfam) pathway is involved in exercise-induced mitochondrial biogenesis. In the present study, nine healthy men performed two 45-min bouts of one-legged knee extension exercise: one bout with restricted blood flow, and the other with nonrestricted blood flow to the working muscle. Muscle biopsies were obtained from the vastus lateralis muscle before exercise and at 0, 30, 120, and 360 min after the exercise bout. Biopsies were analyzed for whole muscle, as well as fiber-type specific mRNA expression of myocyte-enriched calcineurin interacting protein (MCIP)-1, PGC-1α, and downstream mitochondrial transcription factors. A novel finding was that, in human skeletal muscle, PGC-1α mRNA increased more after exercise with restricted blood flow than in the nonrestricted condition. No changes were observed for the mRNA of NRF-1, Tfam, mitochondrial transcription factor B1, and mitochondrial transcription factor B2. Muscle fiber type I and type II did not differ in the basal PGC-1α mRNA levels or in the expression increase after ischemic training. Another novel finding was that there was no difference between the restricted and nonrestricted exercise conditions in the increase of MCIP-1 mRNA, a marker for calcineurin activation. This suggests that calcineurin may be activated by exercise in humans and does not exclude that calcineurin could play a role in PGC-1 transcription activation in human skeletal muscle.

scholarly journals Urea and NaCl regulate UT-A1 urea transporter in opposing directions via TonEBP pathway during osmotic diuresis

2009 ◽  
Vol 296 (1) ◽  
pp. F67-F77 ◽  
Author(s):  
Yu-Mi Kim ◽  
Wan-Young Kim ◽  
Hyun-Wook Lee ◽  
Jin Kim ◽  
H. Moo Kwon ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Plasma Osmolality ◽  
Urea Concentration ◽  
Urea Transporter ◽  
Osmotic Diuresis ◽  
High Salt Diet ◽  
Salt Diet ◽  
Low Protein ◽  
Low Salt ◽  
Urine Concentrating Ability

In our previous studies of varying osmotic diuresis, UT-A1 urea transporter increased when urine and inner medullary (IM) interstitial urea concentration decreased. The purposes of this study were to examine 1) whether IM interstitial tonicity changes with different urine urea concentrations during osmotic dieresis and 2) whether the same result occurs even if the total urinary solute is decreased. Rats were fed a 4% high-salt diet (HSD) or a 5% high-urea diet (HUD) for 2 wk and compared with the control rats fed a regular diet containing 1% NaCl. The urine urea concentration decreased in HSD but increased in HUD. In the IM, UT-A1 and UT-A3 urea transporters, CLC-K1 chloride channel, and tonicity-enhanced binding protein (TonEBP) transcription factor were all increased in HSD and decreased in HUD. Next, rats were fed an 8% low-protein diet (LPD) or a 0.4% low-salt diet (LSD) to decrease the total urinary solute. Urine urea concentration significantly decreased in LPD but significantly increased in LSD. Rats fed the LPD had increased UT-A1 and UT-A3 in the IM base but decreased in the IM tip, resulting in impaired urine concentrating ability. The LSD rats had decreased UT-A1 and UT-A3 in both portions of the IM. CLC-K1 and TonEBP were unchanged by LPD or LSD. We conclude that changes in CLC-K1, UT-A1, UT-A3, and TonEBP play important roles in the renal response to osmotic diuresis in an attempt to minimize changes in plasma osmolality and maintain water homeostasis.

scholarly journals Different Expression of Mitochondrial and Endoplasmic Reticulum Stress Genes in Epicardial Adipose Tissue Depends on Coronary Atherosclerosis

2021 ◽  
Vol 22 (9) ◽  
pp. 4538
Author(s):  
Helena Kratochvílová ◽  
Miloš Mráz ◽  
Barbora J. Kasperová ◽  
Daniel Hlaváček ◽  
Jakub Mahrík ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endoplasmic Reticulum ◽  
Adipose Tissue ◽  
Cardiac Surgery ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Mrna Expression ◽  
Coronary Atherosclerosis ◽  
Stress Genes ◽  
Valvular Surgery

The aim of our study was to analyze mitochondrial and endoplasmic reticulum (ER) gene expression profiles in subcutaneous (SAT) and epicardial (EAT) adipose tissue, skeletal muscle, and myocardium in patients with and without CAD undergoing elective cardiac surgery. Thirty-eight patients, 27 with (CAD group) and 11 without CAD (noCAD group), undergoing coronary artery bypass grafting and/or valvular surgery were included in the study. EAT, SAT, intercostal skeletal muscle, and right atrium tissue and blood samples were collected at the start and end of surgery; mRNA expression of selected mitochondrial and ER stress genes was assessed using qRT-PCR. The presence of CAD was associated with decreased mRNA expression of most of the investigated mitochondrial respiratory chain genes in EAT, while no such changes were seen in SAT or other tissues. In contrast, the expression of ER stress genes did not differ between the CAD and noCAD groups in almost any tissue. Cardiac surgery further augmented mitochondrial dysfunction in EAT. In our study, CAD was associated with decreased expression of mitochondrial, but not endoplasmic reticulum stress genes in EAT. These changes may contribute to the acceleration of coronary atherosclerosis.

TP53 and ATM mRNA expression in skin and skeletal muscle after low-level laser exposure

2017 ◽  
Vol 19 (4) ◽  
pp. 227-231 ◽  
Author(s):  
Luciana Guedes de Almeida ◽  
Luiz Philippe da Silva Sergio ◽  
Flavia de Paoli ◽  
Andre Luiz Mencalha ◽  
Adenilson de Souza da Fonseca
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Laser Exposure ◽  
Low Level ◽  
Low Level Laser ◽  
Level Laser

Global and targeted gene expression and protein content in skeletal muscle of young men following short-term creatine monohydrate supplementation

2008 ◽  
Vol 32 (2) ◽  
pp. 219-228 ◽  
Author(s):  
Adeel Safdar ◽  
Nicholas J. Yardley ◽  
Rodney Snow ◽  
Simon Melov ◽  
Mark A. Tarnopolsky
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Mrna Expression ◽  
Protein Content ◽  
Cellular Response ◽  
Glycogen Synthesis ◽  
Creatine Monohydrate ◽  
Fat Free Mass ◽  
Cell Swelling ◽  
Short Term

Creatine monohydrate (CrM) supplementation has been shown to increase fat-free mass and muscle power output possibly via cell swelling. Little is known about the cellular response to CrM. We investigated the effect of short-term CrM supplementation on global and targeted mRNA expression and protein content in human skeletal muscle. In a randomized, placebo-controlled, crossover, double-blind design, 12 young, healthy, nonobese men were supplemented with either a placebo (PL) or CrM (loading phase, 20 g/day × 3 days; maintenance phase, 5 g/day × 7 days) for 10 days. Following a 28-day washout period, subjects were put on the alternate supplementation for 10 days. Muscle biopsies of the vastus lateralis were obtained and were assessed for mRNA expression (cDNA microarrays + real-time PCR) and protein content (Kinetworks KPKS 1.0 Protein Kinase screen). CrM supplementation significantly increased fat-free mass, total body water, and body weight of the participants ( P < 0.05). Also, CrM supplementation significantly upregulated (1.3- to 5.0-fold) the mRNA content of genes and protein content of kinases involved in osmosensing and signal transduction, cytoskeleton remodeling, protein and glycogen synthesis regulation, satellite cell proliferation and differentiation, DNA replication and repair, RNA transcription control, and cell survival. We are the first to report this large-scale gene expression in the skeletal muscle with short-term CrM supplementation, a response that suggests changes in cellular osmolarity.

scholarly journals Endurance training reduces the contraction-induced interleukin-6 mRNA expression in human skeletal muscle

2004 ◽  
Vol 287 (6) ◽  
pp. E1189-E1194 ◽  
Author(s):  
Christian P. Fischer ◽  
Peter Plomgaard ◽  
Anne K. Hansen ◽  
Henriette Pilegaard ◽  
Bengt Saltin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Muscle Glycogen ◽  
Human Skeletal Muscle ◽  
Acute Exercise ◽  
Glycogen Content ◽  
Knee Extensor ◽  
Exercise Induced ◽  
Response To Exercise ◽  
Resting Muscle

Contracting skeletal muscle expresses large amounts of IL-6. Because 1) IL-6 mRNA expression in contracting skeletal muscle is enhanced by low muscle glycogen content, and 2) IL-6 increases lipolysis and oxidation of fatty acids, we hypothesized that regular exercise training, associated with increased levels of resting muscle glycogen and enhanced capacity to oxidize fatty acids, would lead to a less-pronounced increase of skeletal muscle IL-6 mRNA in response to acute exercise. Thus, before and after 10 wk of knee extensor endurance training, skeletal muscle IL-6 mRNA expression was determined in young healthy men ( n = 7) in response to 3 h of dynamic knee extensor exercise, using the same relative workload. Maximal power output, time to exhaustion during submaximal exercise, resting muscle glycogen content, and citrate synthase and 3-hydroxyacyl-CoA dehydrogenase enzyme activity were all significantly enhanced by training. IL-6 mRNA expression in resting skeletal muscle did not change in response to training. However, although absolute workload during acute exercise was 44% higher ( P < 0.05) after the training period, skeletal muscle IL-6 mRNA content increased 76-fold ( P < 0.05) in response to exercise before the training period, but only 8-fold ( P < 0.05, relative to rest and pretraining) in response to exercise after training. Furthermore, the exercise-induced increase of plasma IL-6 ( P < 0.05, pre- and posttraining) was not higher after training despite higher absolute work intensity. In conclusion, the magnitude of the exercise-induced IL-6 mRNA expression in contracting human skeletal muscle was markedly reduced by 10 wk of training.

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