| Autor: |
Satoh Y; Division of Medicinal Biotechnology, Institute for Medicinal Resources, Graduate School of Pharmaceutical Sciences, The University of Tokushima, Tokushima 770-8505, Japan., Kadota Y, Oheda Y, Kuwahara J, Aikawa S, Matsuzawa F, Doi H, Aoyagi T, Sakuraba H, Itoh K |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of antibiotics [J Antibiot (Tokyo)] 2004 May; Vol. 57 (5), pp. 316-25. |
| DOI: |
10.7164/antibiotics.57.316 |
| Abstrakt: |
The actions of peptidase inhibitors derived from Streptomycete on human cathepsin A (hCath A), yeast carboxypeptidase Y (CPY), and wheat carboxypeptidase II (CPW) were analyzed comparatively. Lactacystin and omuralide (clasto-lactacystin beta-lactone), well-known cytoplasmic proteasome inhibitors, both had a potent and non-competitive inhibitory effect on these homologous serine carboxypeptidases, although they inhibited CPW and hCath A more effectively than CPY in vitro. Ebelactone B exhibited a mixed non-competitive inhibitory effect and selectivity for CPY. Piperastatin A showed competitive inhibition of CPY and hCath A but had little effect on CPW. In contrast, chymostatin inhibited CPW efficiently, while it had less effect on hCath A and CPY. In cell culture system, lactacystin was the most potent as to inactivation of the intralysosomal recombinant hCath A activity expressed in a genetically engineered fibroblastic cell line with galactosialidosis (hCath A deficiency). These results suggest that the specific inhibitory effects of lactacystin and its derivatives on hCath A might be applicable to elucidate the pathophysiological roles in the human deficinecy. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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