title: Effects of inhibitors of the arachidonic acid cascade on primary muscle culture from a Duchenne muscular dystrophy patient.
abstract: The aim of this study was to elucidate the mechanisms of action for potential targets of therapeutic intervention related to the arachidonic acid cascade in muscular dystrophy. Primary cultures from a Duchenne patient were used to study the expression of dystrophin-1, utrophin, desmin, neonatal myosin heavy chain (MHCn) and Bcl-2 during inhibition of phospholipase A2 (PLA2), cyclooxygenase (COX) and lipoxygenase (LOX). Hypo-osmotic treatment was applied in order to trigger Ca2+ influx and PLA2 activity. Inhibition of PLA2 and LOX with prednisolone and nordihydroguaiaretic acid (NDGA) caused a semi-quantitative increase of utrophin and Bcl-2-, and a dose-dependent, quantitative increase of desmin expression, an effect that was augmented by hypo-osmotic treatment. Our results indicate that LOX inhibitors, similarly to corticosteroids, can be beneficial in the treatment of muscular dystrophies.
authors.affiliation: Neuromuscular Unit, Department of Neurology, University Hospital, Linköping University, Linköping SE-58 185, Sweden. istvan.gati@lio.se
authors.forename: I
authors.initials: I
authors.lastname: Gáti
authors.forename: O
authors.initials: O
authors.lastname: Danielsson
authors.forename: T
authors.initials: T
authors.lastname: Betmark
authors.forename: J
authors.initials: J
authors.lastname: Ernerudh
authors.forename: K
authors.initials: K
authors.lastname: Ollinger
authors.forename: N
authors.initials: N
authors.lastname: Dizdar
mesh_terms: D016718:Arachidonic Acid / Q000037:antagonists & inhibitors*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002675:Child, Preschool; D003893:Desmin / Q000096:biosynthesis; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology; D009132:Muscles / Q000166:cytology / Q000187:drug effects; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism*; D009994:Osmolar Concentration; D011239:Prednisolone / Q000494:pharmacology; D049411:Utrophin / Q000096:biosynthesis
chemical_list: D003893:Desmin; D049411:Utrophin; D016718:Arachidonic Acid; D009637:Masoprocol; D011239:Prednisolone; D007213:Indomethacin