Expression and activity of cyclooxygenase isoforms in skeletal muscles and myocardium of humans and rodents.
Conflicting data have been reported on cyclooxygenase (COX)-1 and COX-2 expression and activity in striated muscles, including skeletal muscles and myocardium, in particular it is still unclear whether muscle cells are able to produce prostaglandins (PGs). We characterized the expression and enzymatic activity of COX-1 and COX-2 in the skeletal muscles and in the myocardium of mice, rats and humans. By RT-PCR, COX-1 and COX-2 mRNAs were observed in homogenates of mouse and rat hearts, and in different types of skeletal muscles from all different species. By Western blotting, COX-1 and -2 proteins were detected in skeletal muscles and hearts from rodents, as well as in skeletal muscles from humans. Immunoperoxidase stains showed that COX-1 and -2 were diffusely expressed in the myocytes of different muscles and in the myocardiocytes from all different species. In the presence of arachidonic acid, which is the COX enzymatic substrate, isolated skeletal muscle and heart samples from rodents released predominantly PGE(2). The biosynthesis of PGE(2) was reduced between 50 and 80% (P < 0.05 vs. vehicle) in the presence of either COX-1- or COX-2-selective blockers, demonstrating that both isoforms are enzymatically active. Exogenous PGE(2) added to isolated skeletal muscle preparations from rodents did not affect contraction, whereas it significantly fastened relaxation of a slow type muscle, such as soleus. In conclusion, COX-1 and COX-2 are expressed and enzymatically active in myocytes of skeletal muscles and hearts of rodents and humans. PGE(2) appears to be the main product of COX activity in striated muscles.
Testa
Marco
M
Department of Cardiology, Azienda Ospedaliera Sant'Andrea, Via di Grottarossa 1035, 00189 Roma, Italy. mar.testa@tin.it
Rocca
Bianca
B
Spath
Lucia
L
Ranelletti
Franco O
FO
Petrucci
Giovanna
G
Ciabattoni
Giovanni
G
Naro
Fabio
F
Schiaffino
Stefano
S
Volpe
Massimo
M
Reggiani
Carlo
C
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D015870:Gene Expression; D015971:Gene Expression Regulation, Enzymologic; D006321:Heart / Q000187:drug effects; D006801:Humans; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000201:enzymology; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D009206:Myocardium / Q000166:cytology / Q000201:enzymology*; D032383:Myocytes, Cardiac / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity
D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D016718:Arachidonic Acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone