Prostaglandin E2/cyclooxygenase pathway in human skeletal muscle: influence of muscle fiber type and age

Prostaglandin E₂ (PGE₂) produced by the cyclooxygenase (COX) pathway regulates skeletal muscle protein turnover and exercise training adaptations. The purpose of this study was twofold: 1) define the PGE₂/COX pathway enzymes and receptors in human skeletal muscle, with a focus on type I and II muscle fibers; and 2) examine the influence of aging on this pathway. Muscle biopsies were obtained from the soleus (primarily type I fibers) and vastus lateralis (proportionally more type II fibers than soleus) of young men and women (n = 8; 26 ± 2 yr), and from the vastus lateralis of young (n = 8; 25 ± 1 yr) and old (n = 12; 79 ± 2 yr) men and women. PGE₂/COX pathway proteins [COX enzymes (COX-1 and COX-2), PGE₂ synthases (cPGES, mPGES-1, and mPGES-2), and PGE₂ receptors (EP1, EP2, EP3, and EP4)] were quantified via Western blot. COX-1, cPGES, mPGES-2, and all four PGE₂ receptors were detected in all skeletal muscle samples examined. COX-1 (P < 0.1) and mPGES-2 were ~20% higher, while EP3 was 99% higher and EP4 57% lower in soleus compared with vastus lateralis (P < 0.05). Aging did not change the level of skeletal muscle COX-1, while cPGES increased 45% and EP1 (P < 0.1), EP3, and EP4 decreased ~33% (P < 0.05). In summary, PGE₂ production capacity and receptor levels are different in human skeletal muscles with markedly different type I and II muscle fiber composition. In aging skeletal muscle, PGE₂ production capacity is elevated and receptor levels are downregulated. These findings have implications for understanding the regulation of skeletal muscle adaptations to exercise and aging by the PGE₂/COX pathway and related inhibitors.

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