Effects of inhibitors of the arachidonic acid cascade on primary muscle culture from a Duchenne muscular dystrophy patient.
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.
Gáti
I
I
Neuromuscular Unit, Department of Neurology, University Hospital, Linköping University, Linköping SE-58 185, Sweden. istvan.gati@lio.se
Danielsson
O
O
Betmark
T
T
Ernerudh
J
J
Ollinger
K
K
Dizdar
N
N
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
D003893:Desmin; D049411:Utrophin; D016718:Arachidonic Acid; D009637:Masoprocol; D011239:Prednisolone; D007213:Indomethacin