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.
Lee
Min-Cheol
MC
Department of Pathology,Chonnam National University Medical school and Research Institute of Medical Science, Gwangju, Korea. mclee@chonnam.ac.kr
Wee
Gye-Ryoung
GR
Kim
Jae-Hyoo
JH
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