Indicators of apoptosis in Duchenne muscular dystrophy patients

ABSTRACT

Tissue sections of dystrophic muscle demonstrate apoptotic myonuclei in degenerating muscle fibers of Duchene muscle dystrophy [DMD] patients. The apoptosis cascade can be triggered by 2 main pathways, via an intrinsic, endogenous system such as the mitochondrial Bax/Bcl-2 or via an extrinsic system involving transmembrane receptors of the death receptor family Fas and Fas Ligand [FasL]. The present study is an attempt to demonstrate the levels of Fas and FasL and Bax/Bcl-2 in DMD pathogenesis. Subjects were 16 boys with DMD diagnosed clinically and at the molecular level versus 20 age and socioeconomic matching healthy boys. Plasma DNA fragmentation [0.38% +/- 0.12 vs. 0.2% +/- 0.15] and Fas [9.9 +/- 2.8 vs. 2 +/- 0.1, p < 0.001] together with FasL mRNA expression in circulating lymphocytes [0.47 +/- .09 vs. 0.24 +/- .04, p <0.001] were significantly increased in DMD patients compared to controls. There was a significant increase in Bax mRNA relative concentration [0.19 +/- 0.07 vs. 0.05 +/- 0.01, p <0.00001] accompanied by a significant decrease in Bcl-2 protein in circulating lymphocytes [6.4 +/- 1.6 vs l0 +/- 2.8, p <0.0001] both compared to controls. Indicate that apoptosis and its markers determined in blood of DMD patients can replace the invasive technique of tissue biopsy