Methylprednisolone and membrane properties of primary cultures of mouse spinal cord.
The present study attempts to define the capacity of methylprednisolone sodium succinate (MP) to protect neuronal membranes against a free radical challenge in primary cultures of fetal mouse spinal cord. Incubation of these cultures with MP significantly increased the Na+,K(+)-ATPase activity, an effect that was blocked by the RNA synthesis inhibitor, actinomysin D and the protein synthesis inhibitor, cycloheximide, suggesting an induction of protein synthesis by MP. In contrast, incubation with FeCl2 for 1 or 2 h significantly inhibited Na+,K(+)-ATPase activity and elevated the levels of thiobarbituric acid-reactive substances (TBARS). Pretreatment with MP prevented the rise in TBARS and partially prevented the decrease in Na+,K(+)-ATPase activity for the first hour of FeCl2 incubation, an effect that was lost during the second hour. A second dose of MP after the first hour of incubation with FeCl2 partially restored Na+,K(+)-ATPase activity and reduced TBARS levels after the second hour of exposure to FeCl2. Co-incubation of MP with cycloheximide completely prevented the decrease in Na+,K(+)-ATPase activity seen after a 2-h incubation with FeCl2 and eliminated the need for a second dose of MP after the first hour of incubation with FeCl2. These findings suggest a capacity for rapid protein induction and antioxidant activity for MP in vitro.
Anderson
D K
DK
Cincinnati VA Medical Center, OH.
Dugan
L L
LL
Means
E D
ED
Horrocks
L A
LA
D000818:Animals; D002478:Cells, Cultured; D002712:Chlorides; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D005290:Ferric Compounds / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008566:Membranes / Q000187:drug effects; D008775:Methylprednisolone / Q000494:pharmacology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D012313:RNA / Q000096:biosynthesis; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D013386:Succinates / Q000494:pharmacology; D019802:Succinic Acid; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D002712:Chlorides; D005290:Ferric Compounds; D009419:Nerve Tissue Proteins; D013386:Succinates; D017392:Thiobarbituric Acid Reactive Substances; D003609:Dactinomycin; D012313:RNA; D003513:Cycloheximide; D019802:Succinic Acid; D000254:Sodium-Potassium-Exchanging ATPase; C024555:ferric chloride; D008775:Methylprednisolone