Fluoride and phosphatidylserine induced inhibition of cytosolic insulin-degrading activity.
Cytosol (C) (100,000 x g/60 min, supernatant) from liver, brain and testis (Wistar male rats) are shown to contain insulin degrading activity (C-IDA). The regulation of C-IDA in these fractions by ligands that activate G protein and PKC were examined C-IDA from liver, brain and testis was inhibited 76%; 64% and 50% by 50 mM F- respectively. Chromatography of C fraction from liver on Sephadex G-50 in presence of 1 M (NH4)2SO4 and 20% (v/v) glycerol (experimental condition to remove guanine nucleotides from G proteins) decreased in about 3-fold aluminum fluoride effect on C-IDA. Mg++ (from 5mM to 10 mM) enhanced fluoride effects by inhibiting fully C-IDA. Phosphatidylserine in presence of ATP completely inhibited C-IDA; this inhibition was 31.3% mediated by a phosphorylation reaction. It is concluded that cytosol from different tissues contain proteins capable to associate ligands as aluminum fluoride and PS to regulate C-IDA. It is proposed a mechanism of protein-protein interaction to modulate C-IDA.
Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, Brazil.
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Udrisar
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Wanderley
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000645:Ammonium Sulfate / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D003864:Depression, Chemical; D005459:Fluorides / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D007457:Iodine Radioisotopes; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D010718:Phosphatidylserines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D013737:Testis / Q000187:drug effects / Q000378:metabolism
D007328:Insulin; D007457:Iodine Radioisotopes; D010718:Phosphatidylserines; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D008274:Magnesium; D005459:Fluorides; D000645:Ammonium Sulfate