EFFECTS OF AGING AND EXERCISE TRAINING ON INOS PROTEIN EXPRESSION IN SKELETAL MUSCLE

ABSTRACT Helicobacter pylori infection of the stomach causes an active immune response that includes stimulation of inducible nitric oxide (NO) synthase (iNOS) expression. Although NO can kill H. pylori, the bacterium persists indefinitely, suggesting that NO production is inadequate. We determined if the NO derived from iNOS in macrophages was dependent on the availability of its substrate, l-arginine (l-Arg). Production of NO by H. pylori-stimulated RAW 264.7 cells was dependent on the l-Arg concentration in the culture medium, and the 50% effective dose for l-Arg was 220 μM, which is above reported plasma l-Arg levels. While iNOS mRNA induction was l-Arg independent, iNOS protein increased in an l-Arg-dependent manner that did not involve changes in iNOS protein degradation. l-Lysine, an inhibitor of l-Arg uptake, attenuated H. pylori-stimulated iNOS protein expression, translation, NO levels, and killing of H. pylori. While l-Arg starvation suppressed global protein translation, at concentrations of l-Arg at which iNOS protein was only minimally expressed in response to H. pylori, global translation was fully restored and eukaryotic translation initiation factor α was dephosphorylated. H. pylori lacking the gene rocF, which codes for a bacterial arginase, induced higher levels of NO production by increasing iNOS protein levels. When murine gastric macrophages were activated with H. pylori, supraphysiologic levels of l-Arg were required to permit iNOS protein expression and NO production. These findings indicate that l-Arg is rate limiting for iNOS translation and suggest that the levels of l-Arg that occur in vivo do not permit sufficient NO generation by the host to kill H. pylori.

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Chronic social isolation induces NF-κB activation and upregulation of iNOS protein expression in rat prefrontal cortex

Neurochemistry International ◽

10.1016/j.neuint.2013.06.002 ◽

2013 ◽

Vol 63 (3) ◽

pp. 172-179 ◽

Cited By ~ 30

Author(s):

Jelena Zlatković ◽

Dragana Filipović

Keyword(s):

Prefrontal Cortex ◽

Protein Expression ◽

Social Isolation ◽

Inos Protein ◽

Inos Protein Expression

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Differences in in vitro interactions between macrophages with pathogenic and environmental strains of Prototheca

Future Microbiology ◽

10.2217/fmb-2019-0238 ◽

2020 ◽

Vol 15 (6) ◽

pp. 427-436

Author(s):

Jin Yang ◽

Junhao Zhu ◽

Timothy Kudinha ◽

Fanrong Kong ◽

Qiang-qiang Zhang

Keyword(s):

Protein Expression ◽

Rt Pcr ◽

Inos Protein ◽

Colony Forming Unit ◽

Inos Protein Expression ◽

Cytokine Levels ◽

Different Strains ◽

Different Levels ◽

In Vitro Interactions

Aim: We investigated the interactions between macrophage and different strains of Prototheca. Materials & method: J774A.1 macrophages were infected with clinical isolates of Prototheca ciferrii 18125 and P. ciferrii 50779 and environmental isolate of P. ciferrii N71. Phagocytosis activities were compared by colony-forming unit assays at 3, 6 and 9 h after infection. Cytokine levels were detected by RT-PCR and ELISA. iNOS protein expression was examined by western blotting. Results: All P. ciferrii strains were phagocytized by macrophages but induced different levels of cytokines in macrophages. Moreover, infected by P. ciferrii N71 upregulated much higher iNOS protein expression in J774A.1 than that infected by the clinical strains. Conclusion: Clinical and environmental P. ciferrii strains show differences in their interactions with macrophages, which may be attributed to their virulence.

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Expression of phospholemman and its association with Na+-K+-ATPase in skeletal muscle: effects of aging and exercise training

Journal of Applied Physiology ◽

10.1152/japplphysiol.00375.2005 ◽

2005 ◽

Vol 99 (4) ◽

pp. 1508-1515 ◽

Cited By ~ 29

Author(s):

Justin Reis ◽

Lianqin Zhang ◽

Steve Cala ◽

Korinne N. Jew ◽

Lisa C. Mace ◽

...

Keyword(s):

Skeletal Muscle ◽

Exercise Training ◽

Treadmill Exercise ◽

Accessory Protein ◽

Dependent Manner ◽

Muscle Type ◽

Effects Of Aging ◽

High Level ◽

Reduced Activity ◽

Α Subunits

Phospholemman (PLM) is a recently identified accessory protein of the Na+-K+-ATPase (NKA), with a high level of expression in skeletal muscle. The objectives of this study are to characterize the PLM in skeletal muscle and to test the hypothesis that, as an accessory protein of NKA, expression of PLM and its association with the α-subunits of NKA is regulated during aging and with exercise training. PLM was characterized in skeletal muscle of 6- and 16-mo-old sedentary middle-aged rats (Ms), and the effects of aging and exercise training were studied in Ms, 29-mo-old sedentary senescent, and 29-mo-old treadmill-exercised senescent rats. Expression of PLM was muscle-type dependent, and immunofluorescence study showed that PLM distributed predominantly on the sarcolemmal membrane of the muscle fibers. Anti-PLM antibody reduced activity of NKA, and thus PLM appears to be required for NKA to express its full activity in skeletal muscle. Expression of PLM was not altered with aging but increased after exercise training. Coimmunoprecipitation studies demonstrated that PLM associates with both the α1- and α2-subunit isoforms of NKA. Compared with Ms rats, levels of PLM-associated α1-subunit increased in 29-mo-old sedentary senescent rats, and treadmill exercise has a tendency to partially reverse it. There was no significant change in PLM-associated α2-subunit with age, and exercise training has a tendency to increase that level. It is concluded that, in skeletal muscle, PLM appears to be a protein integral to the NKA complex and that PLM has the potential to modulate NKA in an isoform-specific and muscle type-dependent manner in aging and after exercise training.

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Effects of aging and exercise training on the dynamics of vasoconstriction in skeletal muscle resistance vessels

European Journal of Applied Physiology ◽

10.1007/s00421-017-3541-0 ◽

2017 ◽

Vol 117 (3) ◽

pp. 397-407 ◽

Cited By ~ 4

Author(s):

Elizabeth M. Gittemeier ◽

Tyler Ericson ◽

Payal Ghosh ◽

Steven W. Copp ◽

Alexander B. Opoku-Acheampong ◽

...

Keyword(s):

Skeletal Muscle ◽

Exercise Training ◽

Resistance Vessels ◽

Effects Of Aging

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Combined lack of estrogen receptors a and ? affects vascular iNOS protein expression

Cell and Tissue Research ◽

10.1007/s00441-003-0731-3 ◽

2003 ◽

Vol 313 (1) ◽

pp. 63-70 ◽

Cited By ~ 10

Author(s):

M. Liang ◽

E. Ekblad ◽

M.-L. Lydrup ◽

B.-O. Nilsson

Keyword(s):

Protein Expression ◽

Estrogen Receptors ◽

Inos Protein ◽

Inos Protein Expression

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Aerobic exercise training improves skeletal muscle function and Ca2+ handling-related protein expression in sympathetic hyperactivity-induced heart failure

Journal of Applied Physiology ◽

10.1152/japplphysiol.00281.2010 ◽

2010 ◽

Vol 109 (3) ◽

pp. 702-709 ◽

Cited By ~ 38

Author(s):

C. R. Bueno ◽

J. C. B. Ferreira ◽

M. G. Pereira ◽

A. V. N. Bacurau ◽

P. C. Brum

Keyword(s):

Skeletal Muscle ◽

Exercise Training ◽

Protein Expression ◽

Aerobic Exercise ◽

Muscle Function ◽

Exercise Tolerance ◽

Aerobic Exercise Training ◽

Related Protein ◽

Skeletal Muscle Function ◽

Related Proteins

The cellular mechanisms of positive effects associated with aerobic exercise training on overall intrinsic skeletal muscle changes in heart failure (HF) remain unclear. We investigated potential Ca2+ abnormalities in skeletal muscles comprising different fiber compositions and investigated whether aerobic exercise training would improve muscle function in a genetic model of sympathetic hyperactivity-induced HF. A cohort of male 5-mo-old wild-type (WT) and congenic α2A/α2C adrenoceptor knockout (ARKO) mice in a C57BL/6J genetic background were randomly assigned into untrained and trained groups. Exercise training consisted of a 8-wk running session of 60 min, 5 days/wk (from 5 to 7 mo of age). After completion of the exercise training protocol, exercise tolerance was determined by graded treadmill exercise test, muscle function test by Rotarod, ambulation and resistance to inclination tests, cardiac function by echocardiography, and Ca2+ handling-related protein expression by Western blot. α2A/α2CARKO mice displayed decreased ventricular function, exercise intolerance, and muscle weakness paralleled by decreased expression of sarcoplasmic Ca2+ release-related proteins [α1-, α2-, and β1-subunits of dihydropyridine receptor (DHPR) and ryanodine receptor (RyR)] and Ca2+ reuptake-related proteins [sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)1/2 and Na+/Ca2+ exchanger (NCX)] in soleus and plantaris. Aerobic exercise training significantly improved exercise tolerance and muscle function and reestablished the expression of proteins involved in sarcoplasmic Ca2+ handling toward WT levels. We provide evidence that Ca2+ handling-related protein expression is decreased in this HF model and that exercise training improves skeletal muscle function associated with changes in the net balance of skeletal muscle Ca2+ handling proteins.

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PGC-1α mediates exercise-induced skeletal muscle VEGF expression in mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00076.2009 ◽

2009 ◽

Vol 297 (1) ◽

pp. E92-E103 ◽

Cited By ~ 75

Author(s):

Lotte Leick ◽

Ylva Hellsten ◽

Joachim Fentz ◽

Stine S. Lyngby ◽

Jørgen F. P. Wojtaszewski ◽

...

Keyword(s):

Skeletal Muscle ◽

Exercise Training ◽

Protein Expression ◽

Protein Content ◽

Acute Exercise ◽

Whole Body ◽

Vegf Expression ◽

Vegf Mrna ◽

Exercise Induced ◽

Vegf Protein

The aim of the present study was to test the hypothesis that PGC-1α is required for exercise-induced VEGF expression in both young and old mice and that AMPK activation leads to increased VEGF expression through a PGC-1α-dependent mechanism. Whole body PGC-1α knockout (KO) and littermate wild-type (WT) mice were submitted to either 1) 5 wk of exercise training, 2) lifelong (from 2 to 13 mo of age) exercise training in activity wheel, 3) a single exercise bout, or 4) 4 wk of daily subcutaneous AICAR or saline injections. In skeletal muscle of PGC-1α KO mice, VEGF protein expression was ∼60–80% lower and the capillary-to-fiber ratio ∼20% lower than in WT. Basal VEGF mRNA expression was similar in WT and PGC-1α KO mice, but acute exercise and AICAR treatment increased the VEGF mRNA content in WT mice only. Exercise training of young mice increased skeletal muscle VEGF protein expression ∼50% in WT mice but with no effect in PGC-1α KO mice. Furthermore, a training-induced prevention of an age-associated decline in VEGF protein content was observed in WT but not in PGC-1α KO muscles. In addition, repeated AICAR treatments increased skeletal muscle VEGF protein expression ∼15% in WT but not in PGC-1α KO mice. This study shows that PGC-1α is essential for exercise-induced upregulation of skeletal muscle VEGF expression and for a training-induced prevention of an age-associated decline in VEGF protein content. Furthermore, the findings suggest an AMPK-mediated regulation of VEGF expression through PGC-1α.

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Endurance Exercise Training Up-Regulates Lipolytic Proteins and Reduces Triglyceride Content in Skeletal Muscle of Obese Subjects

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2013-2058 ◽

2013 ◽

Vol 98 (12) ◽

pp. 4863-4871 ◽

Cited By ~ 54

Author(s):

Katie Louche ◽

Pierre-Marie Badin ◽

Emilie Montastier ◽

Claire Laurens ◽

Virginie Bourlier ◽

...

Keyword(s):

Skeletal Muscle ◽

Exercise Training ◽

Protein Expression ◽

Endurance Exercise ◽

Oxidative Capacity ◽

Metabolic Effects ◽

Gene Identification ◽

Mrna Levels ◽

Endurance Exercise Training ◽

Obese Subjects

Context: Skeletal muscle lipase and intramyocellular triglyceride (IMTG) play a role in obesity-related metabolic disorders. Objectives: The aim of the present study was to investigate the impact of 8 weeks of endurance exercise training on IMTG content and lipolytic proteins in obese male subjects. Design and Volunteers: Ten obese subjects completed an 8-week supervised endurance exercise training intervention in which vastus lateralis muscle biopsy samples were collected before and after training. Main Outcome Measures: Clinical characteristics and ex vivo substrate oxidation rates were measured pre- and posttraining. Skeletal muscle lipid content and lipolytic protein expression were also investigated. Results: Our data show that exercise training reduced IMTG content by 42% (P < .01) and increased skeletal muscle oxidative capacity, whereas no change in total diacylglycerol content and glucose oxidation was found. Exercise training up-regulated adipose triglyceride lipase, perilipin (PLIN) 3 protein, and PLIN5 protein contents in skeletal muscle despite no change in mRNA levels. Training also increased hormone sensitive–lipase Ser660 phosphorylation. No significant changes in comparative gene identification 58, G0/G1 switch gene 2, and PLIN2 protein and mRNA levels were observed in response to training. Interestingly, we noted a strong relationship between skeletal muscle comparative gene identification 58 and mitochondrial respiratory chain complex I protein contents at baseline (r = 0.87, P < .0001). Conclusions: Endurance exercise training coordinately up-regulates fat oxidative capacity and lipolytic protein expression in skeletal muscle of obese subjects. This physiological adaptation probably favors fat oxidation and may alleviate the lipotoxic lipid pressure in skeletal muscle. Enhancement of IMTG turnover may be required for the beneficial metabolic effects of exercise in obesity.

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