Long-term growth selection of mice changes the intrinsic susceptibility of myogenic cells to apoptosis.

Abstract

Myogenic cells were derived from mice long-term selected over 70 generations for high 6-weeks body weight (DU-6) and from unselected control mice (DU-Ks). The cells were grown in medium with 10% foetal bovine serum (FBS) for 8 days or transferred to low serum conditions (1% FBS) at days 4 and 6 of cultivation, respectively, and maintained for two further days. In both cell lines, serum reduction induced decreases in DNA and protein contents, and in DNA synthesis rate. It also triggered apoptotic cell death as demonstrated by increased DNA strand breaks and expression of active caspase-3. Concomitantly, the anti-apoptotic protein bcl-2 was enhanced. The basal frequency of apoptotic cells decreased with time of cultivation in both lines and was lower in DU-6 than in DU-Ks cells. However, the increase in apoptosis induced by serum reduction was more pronounced in DU-6 than in DU-Ks cells and did not differ between the time points of serum reduction. The results suggest that growth selection decreases the basal apoptosis frequency of muscle satellite cells under normal supply, but enhances the intrinsic susceptibility to growth factor withdrawal by serum deprivation as a severe apoptotic stimulus. Furthermore, the apoptotic response to growth factor withdrawal seems to be largely independent of the stage of myogenic development.