ABSTRACT
Cellular damage, induced by either A23187 (2×10−5M) or 2,4-dinitrophenol (DNP) (10−3M), has been studied in incubated mouse soleus muscle and has been monitored by electron microscopy and measurement of creatine kinase (CK) efflux. CK efflux induced by DNP was dependent on extracellular Ca, whereas the characteristic myofllament breakdown was not. Chlorpromazine (2 ×10−4M; an inhibitor of phospholipase A (PLA2)) or 5 ×10−6M-nordi-hydroguaiaretic acid (NDGA) (a lipoxygenase inhibitor) almost completely inhibited CK efflux, following treatment with either A23187 or DNP, but did not affect myofilament damage. It is concluded that there are at least two separate pathways in cellular damage: (1) PLA2 activation and lipoxygenase activity culminating in sarco-lemma damage and (2) a system that produces characteristic destruction of the myofilament apparatus.
