The role of NF-kappaB in protein breakdown in immobilization, aging, and exercise: from basic processes to promotion of health.
Between the ages of 20 and 80 years, humans lose about 20-30% of their skeletal muscle weight. This phenomenon has been termed sarcopenia of old age and is directly involved in the well-being of the aged. With aging, people tend to be less mobile and are frequently bedridden, which exacerbates the muscle weight loss. The molecular mechanisms responsible for the muscle protein breakdown during immobilization in aging have been studied in our laboratory in a model of 24-month-old Wistar rats, immobilized for 4 weeks. Subsequently we investigated the activation of the intracellular and extracellular proteolytic systems in the immobilized muscles. A similar group of young (6-month-old) rats was examined and compared to the older rats. The involvement of NF-kappaB transcription factor in muscle atrophy was assessed in immobilized muscles of young and old animals. There were marked differences in the kinetics and the pattern of NF-kappaB activation in young versus old muscles. It seems that in both young and old animals in the early stages of limb immobilization, an alternative pathway of NF-kappaB activation can be observed. However, in late stages of immobilization, the canonic pathway of NF-kappaB activation (p65/p50 complex with I-kappaB alpha degradation) is predominant. Interestingly, the canonic activation pathway is more prominent in muscles from old animals compared to young ones. The activation of NF-kappaB has been observed also in muscles subjected to acute and intense exercise, implying that inflammatory processes may take place under the conditions of intense exercise. This may cause muscle damage and protein breakdown. Therefore, using NF-kappaB pathway inhibitors may prove beneficial in attenuating NF-kappaB-associated muscle damage in both disuse atrophy and strenuous exercise.
Bar-Shai
Marina
M
Department of Anatomy and Cell Biology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, P.O. Box 9649, Haifa 31096, Israel.
Carmeli
Eli
E
Reznick
Abraham Z
AZ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D000818:Animals; D015444:Exercise; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007103:Immobilization; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000502:physiology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606206:Nfkbia protein, rat; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D025801:Ubiquitin; D000072000:NF-KappaB Inhibitor alpha