Myopathy in broiler chickens: a role for Ca(2+)-activated phospholipase A2?
The role of Ca(2+)-dependent phospholipase A2 (PLA2) in the mechanism of skeletal muscle damage in broiler chickens was examined in vitro using a novel, synthetic, PLA2-specific inhibitor Ro31-499/001 (Ro31). Muscle damage was assessed by measurement of creatine kinase (CK) efflux from isolated muscles into the incubation medium. Treatment with the specific Ca(2+)-ionophore 4-Br-A23187 (5 microM) caused a 72% elevation (P<0.05) in muscle 45Ca2+ accumulation, which was associated with a marked increase (P<0.001) in muscle CK efflux (7.6-fold). Incubation with Ro31 (50 microM) reduced (P<0.001) CK efflux from muscles treated with ionophore (45%) but was without effect on 45Ca accumulation. Treatment with the Na+ ionophore monensin (100 microM) induced 55% (P< 0.05) elevation in 45Ca2+ accumulation with a concomitant 2.5-fold increase (P<0.001) in CK loss. Muscles incubated with monensin in the presence of Ro31 exhibited a 49% reduction (P<0.001) in CK leakage but showed no change in 45Ca2+ uptake. The results indicate that increasing external Ca2+ entry, directly or indirectly, and elevation of intracellular Ca2+, significantly alters sarcolemmal integrity resulting in increased CK efflux from broiler skeletal muscle. This process is, at least in part, dependent upon activation of PLA2 activity and thus inhibitable by Ro31. It is further proposed that muscle damage in poultry induced by a range of stresses, and insults may also be mediated by a Ro31 sensitive, PLA2-dependent component. The findings have implications for strategies to reduce or prevent myopathies in poultry affecting bird welfare and product quality.
Sandercock
D A
DA
Roslin Institute (Edinburgh), Roslin, Midlothian EH25 9PS, United Kingdom. dale.sandercock@bbsrc.ac.uk
Mitchell
M A
MA
D000818:Animals; D000001:Calcimycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002645:Chickens; D003402:Creatine Kinase / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007476:Ionophores / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000201:enzymology; D009135:Muscular Diseases / Q000201:enzymology / Q000662:veterinary*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D011201:Poultry Diseases / Q000201:enzymology*
D004791:Enzyme Inhibitors; D007476:Ionophores; D000001:Calcimycin; C033170:4-bromo-A-23187; D003402:Creatine Kinase; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium