Tags

Type your tag names separated by a space and hit enter

NOS3 is involved in the increased protein and arginine metabolic response in muscle during early endotoxemia in mice.
Am J Physiol Endocrinol Metab. 2005 Jun; 288(6):E1258-64.AJ

Abstract

Sepsis is a severe catabolic condition. The loss of skeletal muscle protein mass is characterized by enhanced release of the amino acids glutamine and arginine, which (in)directly affects interorgan arginine and the related nitric oxide (NO) synthesis. To establish whether changes in muscle amino acid and protein kinetics are regulated by NO synthesized by nitric oxide synthase-2 or -3 (NOS2 or NOS3), we studied C57BL6/J wild-type (WT), NOS2-deficient (NOS2-/-), and NOS3-deficient (NOS3-/-) mice under control (unstimulated) and lipopolysaccharide (LPS)-treated conditions. Muscle amino acid metabolism was studied across the hindquarter by infusing the stable isotopes L-[ring-2H5]phenylalanine, L-[ring-2H2]tyrosine, L-[guanidino-15N2]arginine, and L-[ureido-13C,2H2]citrulline. Muscle blood flow was measured using radioactive p-aminohippuric acid dilution. Under baseline conditions, muscle blood flow was halved in NOS2-/- mice (P < 0.1), with simultaneous reductions in muscle glutamine, glycine, alanine, arginine release and glutamic acid, citrulline, valine, and leucine uptake (P < 0.1). After LPS treatment, (net) muscle protein synthesis increased in WT and NOS2-/- mice [LPS vs. control: 13 +/- 3 vs. 8 +/- 1 (SE) nmol.10 g(-1).min(-1) (WT), 18 +/- 5 vs. 7 +/- 2 nmol.10 g(-1).min(-1) (NOS2-/-); P < 0.05 for LPS vs. control]. This response was absent in NOS3-/- mice (LPS vs. control: 11 +/- 4 vs. 10 +/- 2 nmol.10 g(-1).min(-1)). In agreement, the increase in muscle arginine turnover after LPS was also absent in NOS3-/- mice. In conclusion, disruption of the NOS2 gene compromises muscle glutamine release and muscle blood flow in control mice, but had only minor effects after LPS. NOS3 activity is crucial for the increase in muscle arginine and protein turnover during early endotoxemia.

Authors+Show Affiliations

Dept. of Surgery, Maastricht Univ., Maastricht, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15644457

Citation

Luiking, Yvette C., et al. "NOS3 Is Involved in the Increased Protein and Arginine Metabolic Response in Muscle During Early Endotoxemia in Mice." American Journal of Physiology. Endocrinology and Metabolism, vol. 288, no. 6, 2005, pp. E1258-64.
Luiking YC, Hallemeesch MM, Lamers WH, et al. NOS3 is involved in the increased protein and arginine metabolic response in muscle during early endotoxemia in mice. Am J Physiol Endocrinol Metab. 2005;288(6):E1258-64.
Luiking, Y. C., Hallemeesch, M. M., Lamers, W. H., & Deutz, N. E. (2005). NOS3 is involved in the increased protein and arginine metabolic response in muscle during early endotoxemia in mice. American Journal of Physiology. Endocrinology and Metabolism, 288(6), E1258-64.
Luiking YC, et al. NOS3 Is Involved in the Increased Protein and Arginine Metabolic Response in Muscle During Early Endotoxemia in Mice. Am J Physiol Endocrinol Metab. 2005;288(6):E1258-64. PubMed PMID: 15644457.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NOS3 is involved in the increased protein and arginine metabolic response in muscle during early endotoxemia in mice. AU - Luiking,Yvette C, AU - Hallemeesch,Marcella M, AU - Lamers,Wouter H, AU - Deutz,Nicolaas E P, Y1 - 2005/01/11/ PY - 2005/1/13/pubmed PY - 2005/6/17/medline PY - 2005/1/13/entrez SP - E1258 EP - 64 JF - American journal of physiology. Endocrinology and metabolism JO - Am J Physiol Endocrinol Metab VL - 288 IS - 6 N2 - Sepsis is a severe catabolic condition. The loss of skeletal muscle protein mass is characterized by enhanced release of the amino acids glutamine and arginine, which (in)directly affects interorgan arginine and the related nitric oxide (NO) synthesis. To establish whether changes in muscle amino acid and protein kinetics are regulated by NO synthesized by nitric oxide synthase-2 or -3 (NOS2 or NOS3), we studied C57BL6/J wild-type (WT), NOS2-deficient (NOS2-/-), and NOS3-deficient (NOS3-/-) mice under control (unstimulated) and lipopolysaccharide (LPS)-treated conditions. Muscle amino acid metabolism was studied across the hindquarter by infusing the stable isotopes L-[ring-2H5]phenylalanine, L-[ring-2H2]tyrosine, L-[guanidino-15N2]arginine, and L-[ureido-13C,2H2]citrulline. Muscle blood flow was measured using radioactive p-aminohippuric acid dilution. Under baseline conditions, muscle blood flow was halved in NOS2-/- mice (P < 0.1), with simultaneous reductions in muscle glutamine, glycine, alanine, arginine release and glutamic acid, citrulline, valine, and leucine uptake (P < 0.1). After LPS treatment, (net) muscle protein synthesis increased in WT and NOS2-/- mice [LPS vs. control: 13 +/- 3 vs. 8 +/- 1 (SE) nmol.10 g(-1).min(-1) (WT), 18 +/- 5 vs. 7 +/- 2 nmol.10 g(-1).min(-1) (NOS2-/-); P < 0.05 for LPS vs. control]. This response was absent in NOS3-/- mice (LPS vs. control: 11 +/- 4 vs. 10 +/- 2 nmol.10 g(-1).min(-1)). In agreement, the increase in muscle arginine turnover after LPS was also absent in NOS3-/- mice. In conclusion, disruption of the NOS2 gene compromises muscle glutamine release and muscle blood flow in control mice, but had only minor effects after LPS. NOS3 activity is crucial for the increase in muscle arginine and protein turnover during early endotoxemia. SN - 0193-1849 UR - https://www.unboundmedicine.com/medline/citation/15644457/NOS3_is_involved_in_the_increased_protein_and_arginine_metabolic_response_in_muscle_during_early_endotoxemia_in_mice_ DB - PRIME DP - Unbound Medicine ER -