Nitric oxide reverses prednisolone-induced inactivation of muscle satellite cells.
Long-term corticosteroid therapy causes myopathy and can inhibit regeneration of skeletal muscle. Therefore, we hypothesized that corticosteroid exposure reduces satellite cell activity in skeletal myofibers. Male Swiss-Webster mice were injected daily for 8 weeks with prednisolone (GC) or vehicle (control). Single myofibers were isolated from the gastrocnemius, centrifuged to mechanically activate satellite cells, and maintained in culture for 48 h. Both constitutive nitric oxide synthase (NOS) isoforms were reduced in muscle by GC treatment (nNOS: -30%, eNOS: -34%). Fewer myogenic (myoD+) cells emanated from GC myofibers compared to control (-61%, P < 0.05). Supplementation of culture media with the nitric oxide donor, diethylenetriamine NONOate (DETA-NO; 5-50 microM), caused a dose-dependent increase in the number of myoD+ cells arising from both control and GC myofibers (P < 0.05), and 10 and 50 microM DETA-NO eliminated the GC-induced deficit in myogenic cells (P > 0.05). Therefore, supplementation of GC myofibers with DETA-NO restores satellite cell activity to control levels. Nitric oxide production could be an important therapeutic target for the prevention of corticosteroid myopathy.
Betters
Jenna L
JL
Center for Exercise Science, Department of Applied Physiology & Kinesiology, University of Florida, Gainesville, Florida 32611, USA.
Long
Jodi H D
JH
Howe
Kathleen S
KS
Braith
Randy W
RW
Soltow
Quinlyn A
QA
Lira
Vitor A
VA
Criswell
David S
DS
D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005938:Glucocorticoids / Q000494:pharmacology*; D008297:Male; D051379:Mice; D017570:MyoD Protein / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D011239:Prednisolone / Q000494:pharmacology*; D020033:Protein Isoforms / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000187:drug effects*; D014226:Triazenes / Q000494:pharmacology
C105351:1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene; D005938:Glucocorticoids; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D020030:Nitric Oxide Donors; D020033:Protein Isoforms; D014226:Triazenes; D011239:Prednisolone; D019001:Nitric Oxide Synthase