Apoptosis and atrophy in rat slow skeletal muscles in chronic heart failure

• Published in: American Journal of Physiology: Cell Physiology 1999-11, Vol.277 (5), p.C982-C986
• Main Authors: dalla Libera, Luciano, Zennaro, Roberta, Sandri, Marco, Ambrosio, Giovanni Battista, Vescovo, Giorgio
• Format: Article
• Language: English
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.1999.277.5.c982

1  National Research Council Unit for Muscle Biology and Physiopathology, Department of Biomedical Sciences, University of Padova, 35121 Padua; and 2  Internal Medicine I, Venice City Hospital, 30100 Venice, Italy Congestive heart failure is characterized by a skeletal muscle myopathy with muscle bulk loss. The mechanisms responsible for these changes are not clear at present. We have investigated the role of apoptosis in the rat "slow" soleus muscle during the development of heart failure, which was induced by injection of monocrotaline (30 mg/kg). We looked at the time course of apoptosis by studying six animals at each of the following time points: 0, 17, 24, and 30 days. We found a decreased expression of the antiapoptotic protein Bcl-2, which was accompanied by a rise of proapoptotic caspase-3. Ubiquitin levels did not change. DNA nick-end labeling showed an increased number of apoptotic nuclei both in myofibers and interstitial cells when heart failure occurred. At variance with previous observations in the fast-twitch tibialis anterior muscle in the same animals, in which tumor necrosis factor- (TNF- ) increased at the time that apoptosis occurred, the magnitude of apoptosis is lower in soleus muscle and there is no appearance of muscle atrophy. In soleus muscle, apoptosis is accompanied by activation of the caspase-3 system. There is no activation of the TNF- - and ubiquitin-dependent protein waste. In conclusion, slow muscles are less prone to develop apoptosis than fast muscles. Muscle atrophy appears earlier in these latter ones. Bcl-2; caspase-3