ArticlePloS one2015
L-Citrulline Protects Skeletal Muscle Cells from Cachectic Stimuli through an iNOS-Dependent Mechanism.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 51 citations in OpenAlex.
- Effect of Bang® Pre-Workout Master Blaster® combined with four weeks of resistance training on lean body mass, maximal strength, mircoRNA expression, and serum IGF-1 in men: a randomized, double-blind, placebo-controlled trial.Journal of the International Society of Sports Nutrition · 2019Trial
- Potential role of L-citrulline in regulating exercise performance and muscle protein metabolism.NPJ science of food · 2026Review
- Incorporation of microbially salvaged urea-nitrogen into anabolic amino acids during hibernation in arctic ground squirrels.Communications biology · 2026Article
- The Emerging Role of Citrulline and Theanine in Health and Disease: A Comprehensive Review.Nutrients · 2025Review
- Incorporation of microbially salvaged urea-nitrogen into anabolic amino acids during hibernation in arctic ground squirrels.bioRxiv : the preprint server for biology · 2025Article
- Palmitic acid-induced cell death: impact of endoplasmic reticulum and oxidative stress, mitigated by L-citrulline.Animal bioscience · 2025Article
- Type 2 diabetes-related sarcopenia: role of nitric oxide.Nutrition & metabolism · 2024Review
- Effect of synchronicity of amino acid supply on the synthesis of protein in C2C12 myotubes culturedFrontiers in veterinary science · 2024Article
- L-citrulline attenuates lipopolysaccharide-induced inflammatory lung injury in neonatal rats.Pediatric research · 2023Article
- Dietary supplements and vascular function in hypertensive disorders of pregnancy.Pflugers Archiv : European journal of physiology · 2023Review
- Beyond protein synthesis: the emerging role of arginine in poultry nutrition and host-microbe interactions.Frontiers in physiology · 2023Review
- Laparoscopic liver resection is associated with less significant muscle loss than the conventional open approach.World journal of surgical oncology · 2022Article
- Prenatal Exposure to L-Citrulline Has Positive Effects on Reflexive Motor Behavior in Newborn Mice.Archives of Razi Institute · 2022Article
- Article
- Metabolic Profile and Pathological Alterations in the Muscle of Patients with Early-Stage Amyotrophic Lateral Sclerosis.Biomedicines · 2022Article
- Functional roles of taurine, L-theanine, L-citrulline, and betaine during heat stress in poultry.Journal of animal science and biotechnology · 2022Review
- Immunomodulatory and biological properties of helminth-derived small molecules: Potential applications in diagnostics and therapeutics.Frontiers in parasitology · 2022Review
- Dietary L-citrulline modulates the growth performance, amino acid profile, and the growth hormone/insulin-like growth factor axis in broilers exposed to high temperature.Frontiers in physiology · 2022Article
- nNOS-derived NO modulates force production and iNO-derived NO the excitability in C2C12-derived 3D tissue engineering skeletal muscleFrontiers in physiology · 2022Article
- Disrupted NOS2 metabolism drives myoblast response to wasting-associated cytokines.Experimental cell research · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dietary L-citrulline is thought to modulate muscle protein turnover by increasing L-arginine availability. To date, the direct effects of increased L-citrulline concentrations in muscle have been completely neglected. Therefore, we determined the role of L-citrulline in regulating cell size during catabolic conditions by depriving mature C2C12 myotubes of growth factors (serum free; SF) or growth factors and nutrients (HEPES buffered saline; HBS). Cells were treated with L-citrulline or equimolar concentrations of L-arginine (positive control) or L-alanine (negative control) and changes in cell size and protein turnover were assessed. In myotubes incubated in HBS or SF media, L-citrulline improved rates of protein synthesis (HBS: +63%, SF: +37%) and myotube diameter (HBS: +18%, SF: +29%). L-citrulline treatment substantially increased iNOS mRNA expression (SF: 350%, HBS: 750%). The general NOS inhibitor L-NAME and the iNOS specific inhibitor aminoguanidine prevented these effects in both models. Depriving myotubes in SF media of L-arginine or L-leucine, exacerbated wasting which was not attenuated by L-citrulline. The increased iNOS mRNA expression was temporally associated with increases in mRNA of the endogenous antioxidants SOD1, SOD3 and catalase. Furthermore, L-citrulline prevented inflammation (LPS) and oxidative stress (H2O2) induced muscle cell wasting. In conclusion, we demonstrate a novel direct protective effect of L-citrulline on skeletal muscle cell size independent of L-arginine that is mediated through induction of the inducible NOS (iNOS) isoform. This discovery of a nutritional modulator of iNOS mRNA expression in skeletal muscle cells could have substantial implications for the treatment of muscle wasting conditions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.