Fas mediates apoptosis in steroid‐induced myopathy of rats

Abstract

Recently, apoptotic cell death has been reported in differentiated skeletal muscle, where apoptosis was generally assumed not to occur. To investigate whether apoptosis may contribute to the steroid-induced myopathy, rats treated with triamcinolone acetonide (TA) for 9 days were sacrificed for detecting apoptosis by in situ end-labelling (ISEL) and DNA electrophoresis in soleus muscles. Immunohistochemical stainings of Fas antigen and p53 protein were performed to examine whether apoptosis-related proteins were present in the myopathy. Muscle fibre necrosis and apoptotic myonuclei appeared in soleus muscles following administration of TA, while control muscles showed no evidences for apoptosis. Fas antigen was not detected in control muscles, but expressed in soleus muscles of steroid-induced myopathy. Some of the Fas antigen-expressing muscle fibres were positive for ISEL. p53 Protein was not detected in any muscle fibres. These findings indicate that TA can induce apoptosis in differentiated skeletal muscles, and Fas antigen might be partly related to apoptotic muscle death in steroid-induced myopathy.

Significance of Fas receptor protein expression in epithelial ovarian cancer

“…Both FasR and FasL have been identified in lymphoid [23] and epithelial cells. Expression FasR has been demonstrated in renal tubules [24], skeletal muscle [25], smooth and cardiac muscle [26,27], pituitary gland [28], parathyroid gland [29], pancreatic islets [30], hepatocytes [31], testicular germ cells [32], prostatic glands [33], neurons [34], epithelium of fallopian tube [29,35], endometrial glands [29,35], trophoblasts [29,35], bronchial epithelial [29,35] and gastrointestinal-type cells [29,35], chondrocytes [36], thyroid cells [37], and skin [38].…”

Critical illness myopathy: what is happening?

“…Steroid-induced apoptosis may be triggered by Fas-Fas ligand signals involving extrinsic apoptosis pathways [31 ]. Fas-antigen is expressed in diseased but not in normal muscle [59]. Taken together, necrosis, proteolysis and apoptosis can all coincide in steroid-treated muscle.…”

Sensitivity of skeletal muscle to pro-apoptotic factors

“…One of such factors is dexamethasone, a glucocorticoid which induces apoptosis in muscle fibers by activating the mitochondrial pathway and the FAS receptor-dependent pathway. In experiments investigating glucocorticoid-induced apoptosis in rats, an increase in the expression levels of the Fas antigen, caspase-8, as well as Bax, Bad and Bid proteins was noted, whereas no differences were reported in the expression of anti-apoptotic proteins Bcl-2 and Bcl-X L (Lee et al 2001b(Lee et al , 2005. In other studies, an increase in the mitochondrial release of cytochrome C and glucocorticoid-induced activation of caspase-9, caspase-3 and Apaf-1 protein was reported (Chauhan et al 2001, Hoijman et al 2004.…”