title: Effect of cyclooxygenase-2 inhibition by meloxicam, on atrogin-1 and myogenic regulatory factors in skeletal muscle of rats injected with endotoxin.
abstract: Cyclooxygenase-2-induction by inflammatory stimuli has been proposed as a mediator of inflammatory cachexia. We analyse whether cyclooxygenase-2 inhibition by meloxicam administration is able to modify the response of skeletal muscle to inflammation induced by lipopolysaccharide endotoxin (LPS). Male rats were injected with 1 mg kg(-1) LPS at 17:00 h and at 10:00 h the following day, and euthanized 4, 24 or 72 hours later. Atrogin-1, MuRF1, myogenic regulatory factors and cyclooxygenase-2 in the gastrocnemius were determined by real time-PCR (mRNA) and Western blot (protein). In a second experiment the effect of meloxicam administration (1 mg kg⁻¹) was analyzed. Meloxicam was administered either in a preventive manner, 1 hour before each endotoxin injection, or in a therapeutic manner, starting 2 hours after the second LPS injection and at 24 and 48 hours afterwards. There was a marked increase in MuRF1 mRNA (P<0.01) 4 hours after LPS, and in atrogin-1 mRNA 4 hours (P<0.01) and 24 hours (P<0.01) after LPS. Cyclooxygenase-2 was increased, whereas MyoD was decreased at 4, 24 and 72 h. Both types of meloxicam treatment blocked LPS-induced increase in atrogin-1. Preventive, but not therapeutic, meloxicam decreased myostatin (P<0.01) and increased Pax7 (P<0.01) and MyoD (P<0.05). Therapeutic meloxicam treatment decreased gastrocnemius myogenin. These data suggest that cyclooxygenase-2 inhibition by meloxicam administration can prevent the increase in atrogin-1 and the decrease in MyoD induced by LPS administration. However, prolonged therapeutic meloxicam treatment seems to be less effective, since it can inhibit myogenic regulatory factors.
authors: Department of Physiology, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain.
authors: A I
authors: AI
authors: Martin
authors: M P
authors: MP
authors: Nieto-Bona
authors: E
authors: E
authors: Castillero
authors: C
authors: C
authors: Fernandez-Galaz
authors: M
authors: M
authors: Lopez-Menduina
authors: A B
authors: AB
authors: Gomez-Sanmiguel
authors: C
authors: C
authors: Gomez-Moreira
authors: M Angeles
authors: MA
authors: Villanua
authors: A
authors: A
authors: Lopez-Calderon
mesh_terms: D000818:Animals; D015153:Blotting, Western; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D000077239:Meloxicam; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism*; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D013997:Time Factors; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D008070:Lipopolysaccharides; D009124:Muscle Proteins; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D018006:Myogenic Regulatory Factors; C530821:PAX7 protein, rat; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D013843:Thiazines; D013844:Thiazoles; D000070584:Tripartite Motif Proteins; C482199:lipopolysaccharide, E coli O55-B5; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; C486692:Fbxo32 protein, rat; D044843:SKP Cullin F-Box Protein Ligases; C499086:Trim63 protein, rat; D044767:Ubiquitin-Protein Ligases; D000077239:Meloxicam