Apoptosis of skeletal muscle on steroid-induced myopathy in rats.
Apoptotic cell death of differentiated skeletal muscle has been reported in an experimental steroid-induced myopathy of rats. To investigate the underlying molecular changes in the apoptosis of skeletal muscle, in situ end labeling (ISEL), Fas expression, and Western blot analysis for apoptosis-related proteins in the soleus muscle of triamcinolone acetonide (TA)-induced myopathy of rats were studied. Proteins for Western blot analysis included Fas-associated death domain (FADD) and caspase 8 for extrinsic pathway, as well as Bcl-2, Bcl-XL, Bax, Bad, Bid, Akt, p-Akt, and caspase 9 for intrinsic pathway. ISEL-positive myonuclei in TA-treated rats were 1.8 +/- 1.2%, whereas Fas-positive muscle fibers were 4.5 +/- 2.0%. One-fourth of Fas-positive muscle fibers had ISEL-positive myonuclei. Levels of FADD, Bax, Bad, and Bid were substantially increased in the TA-induced myopathy group, whereas Bcl-2, Bcl-XL, Akt, p-Akt, and caspase 9 did not change between control and myopathy groups. Caspase 8 activity increased in the myopathy group. These findings indicate that apoptosis of skeletal muscle in TA-induced myopathy may be triggered by Fas-Fas ligand signals and promoted mainly by overexpression of the pro-apoptotic molecules of FADD and caspase 8 involving the extrinsic pathway. The apoptotic process presented in this study supports a direct, nongenomic effect of a glucocorticoid on cellular membranes leading to cellular apoptosis rather than genomic effector mechanism of steroid hormone mediated by cytosolic steroid receptors.
Department of Pathology,Chonnam National University Medical school and Research Institute of Medical Science, Gwangju, Korea. mclee@chonnam.ac.kr
Min-Cheol
MC
Lee
Gye-Ryoung
GR
Wee
Jae-Hyoo
JH
Kim
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D004195:Disease Models, Animal; D005260:Female; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology*; D009135:Muscular Diseases / Q000139:chemically induced* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014222:Triamcinolone Acetonide / Q000633:toxicity*
D000893:Anti-Inflammatory Agents; D014222:Triamcinolone Acetonide