Metabolism and degradation products of recombinant human insulin-like growth factor-I in lysosomes of rat kidney
| Autor: | Kimura T, Tamoto H, Tanaka Y, Tozuka Z, Sato A |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
Leupeptins Health Toxicology and Mutagenesis Molecular Sequence Data Peptide Cysteine Proteinase Inhibitors Kidney Toxicology Biochemistry Amino Acid Chloromethyl Ketones law.invention Rats Sprague-Dawley chemistry.chemical_compound law Animals Humans Insulin Amino Acid Sequence Insulin-Like Growth Factor I Chromatography High Pressure Liquid Pharmacology chemistry.chemical_classification Serine protease Cathepsin biology Molecular mass Leupeptin General Medicine Glutathione Cysteine protease Peptide Fragments Recombinant Proteins Rats Microscopy Electron chemistry biology.protein Recombinant DNA Lysosomes Sequence Analysis Proinsulin |
| Zdroj: | Xenobiotica. 29:281-295 |
| ISSN: | 1366-5928 0049-8254 |
| DOI: | 10.1080/004982599238678 |
| Popis: | 1. The degradation of recombinant human insulin-like growth factor-I (rhIGF-I) by purified lysosomes of rat kidney was examined in vitro. The peptide structures of the 13 degradation products were deduced from the sequence analysis and the molecular mass. Rat kidney lysosomal cathepsins efficiently cleave rhIGF-I to two chain peptides, like insulin. The cleavages mainly occur at the C-peptide/A-chain junction, D-peptide/A-chain junction and B21-22 or B22-23. 2. The effect of inhibitors on the lysosomal degradation of rhIGF-I was examined semiquantitatively by the rate of formation of the degradation products. The degradation of rhIGF-I was almost completely inhibited by the lysosomal cysteine protease inhibitors, leupeptin and leucine chloromethyl ketone, and a serine protease inhibitor, phenylmethylsulphonyl fluoride. On the other hand, the degradation was enhanced by the addition of a reducing agent, glutathione. |
| Databáze: | OpenAIRE |
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