Prostaglandin E 2 / cyclooxygenase pathway in human skeletal muscle : 4 Influence of muscle fiber type and age

41 Prostaglandin E2 (PGE2) produced by the cyclooxygenase (COX) pathway regulates 42 skeletal muscle protein turnover and exercise training adaptations. The purpose of this 43 study was two-fold: 1) Define the PGE2/COX pathway enzymes and receptors in human 44 skeletal muscle, with a focus on Type I and II muscle fibers, 2) Examine the influence of 45 aging on this pathway. Muscle biopsies were obtained from the soleus (primarily Type I 46 fibers) and vastus lateralis (proportionally more Type II fibers than soleus) of young men 47 and women (n=8, 26±2y), and from the vastus lateralis of young (n=8; 25±1y) and old 48 (n=12; 79±2y) men and women. PGE2/COX pathway proteins [COX enzymes (COX-1, 49 COX-2), PGE2 synthases (cPGES, mPGES-1, mPGES-2), and PGE2 receptors (EP1, 50 EP2, EP3, EP4)] were quantified via Western blot. COX-1, cPGES, mPGES-2, and all 51 four PGE2 receptors were detected in all skeletal muscle samples examined. COX-1 52 (P<0.1) and mPGES-2 were ~20% higher, while EP3 was 99% higher and EP4 57% lower 53 in soleus compared to vastus lateralis (P<0.05). Aging did not change the level of skeletal 54 muscle COX-1, while cPGES increased 45% and EP1 (P<0.1), EP3, and EP4 decreased 55 ~33% (P<0.05). In summary, PGE2 production capacity and receptor levels are different in 56 human skeletal muscles with markedly different Type I and II muscle fiber composition. In 57 aging skeletal muscle, PGE2 production capacity is elevated and receptor levels are 58 downregulated. These findings have implications for understanding the regulation of 59 skeletal muscle adaptations to exercise and aging by the PGE2/COX pathway and related 60 inhibitors. 61 62 63