المؤلفون: Paul B. Gordon, Per Ottar Seglen

المصدر: Archives of Biochemistry and Biophysics. 217:282-294

مصطلحات موضوعية: Male, Adenosine, Biophysics, Endogeny, Puromycin Aminonucleoside, Biology, Protein degradation, Biochemistry, chemistry.chemical_compound, Adenosine Triphosphate, medicine, Protein biosynthesis, Animals, Purine metabolism, Molecular Biology, chemistry.chemical_classification, Dose-Response Relationship, Drug, Mercaptopurine, Adenine, Autophagy, Proteins, Rats, Inbred Strains, Riboside, Rats, Amino acid, Liver, chemistry, Purines, Lysosomes, medicine.drug

الوصف: About 100 different purine derivatives and analogs were tested for their effect on protein synthesis and protein degradation in isolated rat hepatocytes. These included 6-aminopurines (adenine and adenosine analogs), 6-mercaptopurines, chloropurines, oxypurines, cytokinins, methylxanthines, methylindoles, benzimidazoles, and benzodiazepines. Most of the compounds were either inactive or inhibited protein synthesis as much as or more than they inhibited protein degradation. However, three methylated 6-aminopurines (3-methyladenine, 6-dimethylaminopurine riboside, and puromycin aminonucleoside) and four 6-mercaptopurines (6-methylmercaptopurine, 6-methylmercaptopurine riboside, 6-mercaptopurine riboside, and 2′,3′,5t - triacetyl-6-mercaptopurine riboside) had a markedly stronger effect on protein degradation than on synthesis, and might therefore be potentially useful as selective degradation inhibitors. None of the seven above-mentioned purines had any significant effect on the degradation of the exogenous protein, asialofetuin, and would therefore seem to selectively inhibit endogenous protein degradation. Since the degradation was not further affected by purines in the presence of amino acids or lysosomotropic amines, it is suggested that the purines exert their effect specifically upon the autophagic/lysosomal pathway. All the mercaptopurines significantly depressed cellular ATP levels, whereas the methylated aminopurines did not. For this reason, the latter are probably more useful as degradation inhibitors. 3-Methyladenine had no effect on protein synthesis at a concentration (5 m m ) which inhibited protein degradation by more than 60%, and may therefore be regarded as a highly specific inhibitor of autophagy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cbb3d1d32cf246940c91647e9d840220Test
https://doi.org/10.1016/0003-9861Test(82)90504-5

المؤلفون: Amy C. Munthe-Kaas, Mary Ann S. Dybedal, Per Ottar Seglen

المصدر: Experimental Cell Research. 155:121-128

مصطلحات موضوعية: Leupeptins, Proteolysis, Chronic lymphocytic leukemia, Lymphocyte, Endogeny, Protein degradation, Biology, chemistry.chemical_compound, Phagocytosis, Autophagy, medicine, Humans, Lymphocytes, Amino Acids, chemistry.chemical_classification, Propylamines, medicine.diagnostic_test, Adenine, Leupeptin, Proteins, Cell Biology, medicine.disease, Leukemia, Lymphoid, Neoplasm Proteins, Amino acid, medicine.anatomical_structure, chemistry, Biochemistry, Cytoplasm, Lysosomes

الوصف: Lymphocytes from normal human subjects and from patients with chronic lymphocytic leukemia were found to degrade their endogenous protein at similar rates (2.5–3.0%/h) when incubated in an amino acid-free buffer. Protein degradation was inhibited 20–35 % by inhibitors of autophagic sequestration (amino acids, 3-methyladenine) and by inhibitors of intra-lysosomal proteolysis (leupeptin, propylamine), the extent of inhibition being similar in normal and leukemic lymphocytes. The inhibitor effects, together with the electronmicroscopic demonstration of autophagosomes in the lymphocyte cytoplasm, is taken as evidence for the existence of an autophagic-lysosomal pathway in human lymphocytes, potentially responsible for as much as one-third of their overall protein degradation.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dc496afd1eb90b5bb6fc506dc9d3968eTest
https://doi.org/10.1016/0014-4827Test(84)90773-0

المؤلفون: P. B. Gordon, Per Ottar Seglen

مصطلحات موضوعية: Purine, Liver cytology, Protein degradation, Biology, chemistry.chemical_compound, Adenosine Triphosphate, Phagocytosis, Protein biosynthesis, Animals, Amino Acids, Biological Sciences: Cell Biology, Cells, Cultured, chemistry.chemical_classification, Multidisciplinary, Adenine, Autophagy, Proteins, Cell biology, Amino acid, Rats, Biochemistry, chemistry, Liver, Protein Biosynthesis, Autolysis, Lysosomes, Adenosine triphosphate, Intracellular

الوصف: 3-Methyladenine (5 mM) inhibits endogenous protein degradation in isolated rat hepatocytes by about 60%, while having no adverse effect on the degradation of an exogenous protein (asialofetuin), on protein synthesis, or on intracellular ATP levels. 3-Methyladenine appears to act specifically upon the autophagic/lysosomal pathway of degradation, as judged from its lack of effect in the presence of amino acids or a lysosomotropic amine (propylamine). The effect of the purine is not mediated by amino acids because the inhibition of protein degradation is accompanied by a significant depression of intracellular amino acid levels. The ability of 3-methyladenine to suppress the formation of electron microscopically visible autophagosomes suggests that it may be regarded as a specific inhibitor of autophagy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ce1babbf577c2810d389d0036c16cd81Test
https://europepmc.org/articles/PMC346086Test/