Lead-induced inclusion bodies: composition and probable role in lead metabolism.
Lead-induced inclusion bodies in renal tubular cells of rats have been studied in vitro after isolation by differential centrifugation. The inclusion bodies are insoluble in physiological media but may be dissolved in denaturants like 6M urea and sodium deoxycholate. They contain about 40-50 mug of lead/mg protein, but only about 10% of this is tightly bound. They also contain calcium, iron, zinc, copper, and cadmium. The protein is rich in glutamic and aspartic acids, glycine and cystine. When dissolved in 6M urea, the protein migrates as a single band on acrylamide gel electrophoresis and has a molecular weight of 27,500. It is suggested that the inclusion bodies function as an intracellular depot of nondiffusible lead. Further studies have been directed toward finding a free, unaggregated lead-containing protein fraction. Nuclear proteins from kidneys of lead-toxic rats were separated into NaCl-, Tris-, and NaOH-soluble fractions and an insoluble acidic fraction. A quantitatively small lead-containing protein was found in the 0.14M NaCl fraction. Amino acid composition, electrophoretic mobility, molecular weight, and ability to bind lead are similar to those of insoluble inclusion body protein. The possible role of this soluble lead-binding protein in the formation of nuclear inclusion bodies is at present time not certain. These studies do suggest, however, that protein-bound lead in renal tubular cells may be partitioned between insoluble and nondiffusible morphologically discrete inclusion bodies and a soluble, extractable fraction which is presumably diffusable.
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D066298:In Vitro Techniques; D002479:Inclusion Bodies / Q000032:analysis / Q000187:drug effects*; D007684:Kidney Tubules / Q000473:pathology; D007854:Lead / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008670:Metals / Q000032:analysis; D008854:Microscopy, Electron; D008970:Molecular Weight; D009698:Nucleoproteins; D011485:Protein Binding; D051381:Rats; D012965:Sodium Chloride; D014508:Urea
D000596:Amino Acids; D008670:Metals; D009698:Nucleoproteins; D007854:Lead; D012965:Sodium Chloride; D014508:Urea