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

Abstract

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.