Lipopolysaccharide stimulates nitric oxide synthase-2 expression in murine skeletal muscle and C2C12myoblasts via Toll-like receptor-4 and c-Jun NH2-terminal kinase pathways

2004 ◽  
Vol 287 (6) ◽  
pp. C1605-C1615 ◽  
Author(s):  
Robert A. Frost ◽  
Gerald J. Nystrom ◽  
Charles H. Lang
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Nitric Oxide Synthase ◽  
Mrna Expression ◽  
Dominant Negative ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Tlr4 Mrna ◽  
Oxide Synthase

The inducible form of nitric oxide synthase (NOS2) catalyzes the synthesis of nitric oxide (NO) from arginine in response to injury and infection. NOS2 is expressed predominantly by macrophages and lymphocytes. However, skeletal muscle also expresses NOS2 in response to inflammatory stimuli. The present study sought to determine whether lipopolysaccharide (LPS) stimulates NOS2 in skeletal muscle via Toll-like receptor-4 (TLR4). Intraperitoneal injection of LPS in wild-type mice (C3H/HeSnJ) increased NOS2 mRNA fourfold in skeletal muscle, while no change in NOS2 mRNA was observed in C3H/HeJ mice that harbored a mutation in the LPS receptor. NOS2 coimmunoprecipitated with the muscle-specific caveolin-3 protein, suggesting that myofibers per se respond to LPS in vivo. LPS stimulated NOS2 mRNA expression in C2C12myocytes, and the regulation of NOS2 mRNA was comparable in myoblasts and differentiated myotubes. LPS transiently stimulated the phosphorylation of the interleukin-1 receptor-associated kinase (IRAK-1) in C2C12cells and decreased the total amount of IRAK-1 both in vitro and in vivo over time. LPS stimulated the expression of an NF-κβ reporter plasmid, and this was inhibited by the proteasomal inhibitor MG-132. Both myoblasts and myotubes expressed TLR2 and TLR4 mRNA. Expression of a dominant negative form of TLR4 in C2C12cells blocked LPS-induced NF-κβ reporter activity. SP-600125 [a c-Jun NH2-terminal kinase (JNK) inhibitor] also prevented LPS stimulation of NOS2 expression. Moreover, the JNK inhibitor prevented the LPS-induced increase in NO synthesis. These data indicate that LPS increases NOS2 mRNA expression in muscle via a TLR4-dependent mechanism.

Toll-like receptor 4 mediates ozone-induced murine lung hyperpermeability via inducible nitric oxide synthase

2001 ◽  
Vol 280 (2) ◽  
pp. L326-L333 ◽  
Author(s):  
Steven R. Kleeberger ◽  
Sekhar P. M. Reddy ◽  
Liu-Yi Zhang ◽  
Hye-Youn Cho ◽  
Anne E. Jedlicka
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Specific Inhibitor ◽  
Mrna Levels ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Tlr4 Mrna ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

We tested the hypotheses that 1) inducible nitric oxide synthase (iNOS) mediates ozone (O3)-induced lung hyperpermeability and 2) mRNA levels of the gene for iNOS ( Nos2) are modulated by Toll-like receptor 4 ( Tlr4) during O3exposure. Pretreatment of O3-susceptible C57BL/6J mice with a specific inhibitor of total NOS ( NG-monomethyl-l-arginine) significantly decreased the mean lavageable protein concentration (a marker of lung permeability) induced by O3(0.3 parts/million for 72 h) compared with vehicle control mice. Furthermore, lavageable protein in C57BL/B6 mice with targeted disruption of Nos2 [ Nos2(−/−)] was 50% less than the protein in wild-type [ Nos2(+/+)] mice after O3. To determine whether Tlr4 modulates Nos2 mRNA levels, we studied C3H/HeJ (HeJ) and C3H/HeOuJ mice that differ only at a missense mutation in Tlr4 that confers resistance to O3-induced lung hyperpermeability in the HeJ strain. Nos2 and Tlr4 mRNA levels were significantly reduced and correlated in resistant HeJ mice after O3relative to those in susceptible C3H/HeOuJ mice. Together, the results are consistent with an important role for iNOS in O3-induced lung hyperpermeability and suggest that Nos2 mRNA levels are mediated through Tlr4.

scholarly journals Expression of nitric oxide synthase isoforms in the mouse kidney: cellular localization and influence by lipopolysaccharide and Toll-like receptor 4

2006 ◽  
Vol 36 (8-9) ◽  
pp. 499-516 ◽  
Author(s):  
Bo Holmqvist ◽  
Christina Falk Olsson ◽  
Maj-Lis Svensson ◽  
Catharina Svanborg ◽  
Johan Forsell ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Cellular Localization ◽  
Mouse Kidney ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Oxide Synthase

scholarly journals Endothelial nitric oxide synthase is central to skeletal muscle metabolic regulation and enzymatic signaling during exercise in vivo

2010 ◽  
Vol 298 (5) ◽  
pp. R1399-R1408 ◽  
Author(s):  
Robert S. Lee-Young ◽  
Julio E. Ayala ◽  
Charles F. Hunley ◽  
Freyja D. James ◽  
Deanna P. Bracy ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Metabolic Regulation ◽  
Acid Uptake ◽  
Enos Expression ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Endothelial nitric oxide synthase (eNOS) is associated with a number of physiological functions involved in the regulation of metabolism; however, the functional role of eNOS is poorly understood. We tested the hypothesis that eNOS is critical to muscle cell signaling and fuel usage during exercise in vivo, using 16-wk-old catheterized (carotid artery and jugular vein) C57BL/6J mice with wild-type (WT), partial (+/−), or no expression (−/−) of eNOS. Quantitative reductions in eNOS expression (∼40%) elicited many of the phenotypic effects observed in enos−/− mice under fasted, sedentary conditions, with expression of oxidative phosphorylation complexes I to V and ATP levels being decreased, and total NOS activity and Ca2+/CaM kinase II Thr286 phosphorylation being increased in skeletal muscle. Despite these alterations, exercise tolerance was markedly impaired in enos−/− mice during an acute 30-min bout of exercise. An eNOS-dependent effect was observed with regard to AMP-activated protein kinase signaling and muscle perfusion. Muscle glucose and long-chain fatty acid uptake, and hepatic and skeletal muscle glycogenolysis during the exercise bout was markedly accelerated in enos−/− mice compared with enos+/− and WT mice. Correspondingly, enos−/− mice exhibited hypoglycemia during exercise. Thus, the ablation of eNOS alters a number of physiological processes that result in impaired exercise capacity in vivo. The finding that a partial reduction in eNOS expression is sufficient to induce many of the changes associated with ablation of eNOS has implications for chronic metabolic diseases, such as obesity and insulin resistance, which are associated with reduced eNOS expression.

Upregulation of neuronal nitric oxide synthase in skeletal muscle by swim training

2000 ◽  
Vol 279 (4) ◽  
pp. H1757-H1766 ◽  
Author(s):  
Rabelais Tatchum-Talom ◽  
Richard Schulz ◽  
J. Robert McNeill ◽  
Fadi H. Khadour
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Similar Degree ◽  
Mesenteric Arterial Bed ◽  
Neuronal Nos ◽  
Oxide Synthase

Exercise enhances cardiac output and blood flow to working skeletal muscles but decreases visceral perfusion. The alterations in nitric oxide synthase (NOS) activity and/or expression of the cardiopulmonary, skeletal muscle, and visceral organs induced by swim training are unknown. In sedentary and swim-trained rats (60 min twice/day for 3–4 wk), we studied the alterations in NOS in different tissues along with hindquarter vasoreactivity in vivo during rest and mesenteric vascular bed reactivity in vitro. Hindquarter blood flow and conductance were reduced by norepinephrine in both groups to a similar degree, whereas N G-nitro-l-arginine methyl ester reduced both indexes to a greater extent in swim-trained rats. Vasodilator responses to ACh, but not bradykinin or S-nitroso- N-acetyl-penicillamine, were increased in swim-trained rats. Ca2+-dependent NOS activity was enhanced in the hindquarter skeletal muscle, lung, aorta, and atria of swim-trained rats together with increased expression of neuronal NOS in the hindquarter skeletal muscle and endothelial NOS in the cardiopulmonary organs. Mesenteric arterial bed vasoreactivity was unaltered by swim training. Physiological adaptations to swim training are characterized by enhanced hindquarter ACh-induced vasodilation with upregulation of neuronal NOS in skeletal muscle and endothelial NOS in the lung, atria, and aorta.

scholarly journals Bacterial Lipopolysaccharide Signaling Through Toll-Like Receptor 4 Suppresses Asthma-Like Responses Via Nitric Oxide Synthase 2 Activity

2003 ◽  
Vol 171 (2) ◽  
pp. 1001-1008 ◽  
Author(s):  
Dunia Rodríguez ◽  
Alexandre C. Keller ◽  
Eliana L. Faquim-Mauro ◽  
Mahasti S. de Macedo ◽  
Fernando Q. Cunha ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Bacterial Lipopolysaccharide ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Nitric Oxide Synthase 2 ◽  
Oxide Synthase
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