TNF-alpha is involved in activating DNA fragmentation in skeletal muscle.
Intraperitoneal administration of 100 microg kg(-1) (body weight) of tumour necrosis factor-alpha to rats for 8 consecutive days resulted in a significant decrease in protein content, which was concomitant with a reduction in DNA content. Interestingly, the protein/DNA ratio was unchanged in the skeletal muscle of the tumour necrosis factor-alpha-treated animals as compared with the non-treated controls. Analysis of muscle DNA fragmentation clearly showed enhanced laddering in the skeletal muscle of tumour necrosis factor-alpha-treated animals, suggesting an apoptotic phenomenon. In a different set of experiments, mice bearing a cachexia-inducing tumour (the Lewis lung carcinoma) showed an increase in muscle DNA fragmentation (9.8-fold) as compared with their non-tumour-bearing control counterparts as previously described. When gene-deficient mice for tumour necrosis factor-alpha receptor protein I were inoculated with Lewis lung carcinoma, they were also affected by DNA fragmentation; however the increase was only 2.1-fold. These results suggest that tumour necrosis factor-alpha partly mediates DNA fragmentation during experimental cancer-associated cachexia.
Carbó
N
N
Cancer Research Group, Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Diagonal 645, 08028-Barcelona, Spain.
Busquets
S
S
van Royen
M
M
Alvarez
B
B
López-Soriano
F J
FJ
Argilés
J M
JM
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D017209:Apoptosis; D002100:Cachexia / Q000209:etiology*; D018827:Carcinoma, Lewis Lung / Q000097:blood / Q000150:complications / Q000473:pathology; D053938:DNA Fragmentation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000502:physiology*
D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha