| Autor: |
F J Ballard, G L Francis, S E Knowles |
| Rok vydání: |
2008 |
| Předmět: |
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| Zdroj: |
Ciba Foundation Symposium 75-Protein Degradation in Health and Disease |
| DOI: |
10.1002/9780470720585.ch8 |
| Popis: |
In experiments involving a range of cultured mammalian cells derived from several different tissues we have shown that lysosomotropic agents such as proteolytic inhibitors or weak bases are only able to reduce intracellular protein breakdown by about 30% (Knowles and Ballard 1976; Ballard 1977; Hopgood and Ballard 1980; Livesey et al. 1980). A similar maximal extent of inhibition is observed with growth factors and protein synthesis inhibitors, agents that are also thought to act on lysosomal proteolysis (Ballard 1977; Ballard et al. 1980). Furthermore, combinations of these different compounds are no more effective than any one effective agent added at an optimal concentration. Consequently, we have proposed that lysosomal protein breakdown only accounts for about a third of the total rate of intracellular protein breakdown. This value is almost certainly an upper limit produced by carrying out the experiments in serum-free medium, because lysosomotropic agents are usually without effect on protein breakdown when tested on cells incubated in normal growth medium containing 10% of fetal calf serum (unpublished data). A second difficulty with a lysosomal pathway of intracellular proteolysis is explaining how it could be compatible with the widely different half-lives of cell proteins (Goldberg and St. John 1976). Some type of selective uptake of proteins having short half-lives or selective exclusion of proteins with long half-lives must be proposed. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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