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: Per Ottar Seglen, Atilla L. Kovács, Katalin Molnár

المصدر: FEBS letters. 134(2)

مصطلحات موضوعية: Male, Adenosine, Biophysics, Endogeny, Biology, Protein degradation, Puromycin Aminonucleoside, Biochemistry, chemistry.chemical_compound, Phagocytosis, Structural Biology, Genetics, medicine, Autophagy, Animals, Purine metabolism, Molecular Biology, chemistry.chemical_classification, Proteins, Rats, Inbred Strains, Cell Biology, Riboside, Amino acid, Rats, Mechanism of action, chemistry, Liver, Vacuoles, Puromycin, medicine.symptom, Lysosomes, medicine.drug

الوصف: Some methylated adenosine derivatives, most notably 6-dimethylaminopurine riboside and puromycin aminonucleoside, have been shown to inhibit the autophagic/lysosomal pathway of endogenous protein degradation in isolated rat hepatocytes [ 11. The mechanism of action of these methylaminopurines is not known. One possibility is that they might exert their effect by preventing the first reaction in the autophagic sequence, i.e., the sequestration of cytoplasmic material into autophagosomes [2], as do the amino acids [3-61. Another possibility is that the purines might interfere with the further processing of the autophagosomes, including their fusion with lysosomes, as seems to be the case with most other degradation inhibitors [7]. To distinguish between these two possibilities, we have undertaken a correlated biochemical and morphometric analysis of the effects of several adenine and adenosine derivatives. The results indicate that the methylated aminopurines inhibit endogenous protein degradation at the level of autophagic sequestration.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5036a22588df243803779a6b2a5e944fTest
https://pubmed.ncbi.nlm.nih.gov/7308488Test