herbimycin and Albuminuria

Albuminuria represents one of the most unfavourable diagnostic factors for the prognosis of nephropathies. We investigated albumin-induced NF-kappaB activation and the potential contribution of tyrosine kinase and protein kinase C. Therefore we exposed proximal tubule-derived human (IHKE-1), opossum (OK) and porcine (LLC-PK1) cell lines to serum albumin at concentrations of 10 - 500 mg/l. DNA-binding activity of NF-kappaB increased concentration-dependently in the presence of albumin. In OK and LLC-PK1 cells, NF-kappaB activity increased during the first 45 min and reached a plateau thereafter. In IHKE-1, cells NF-kappaB activity reached a plateau after 90 min with a maximum at 180 min exposure to albumin. The albumin-induced increase in NF-kappaB DNA-binding activity was inhibited by herbimycin A (tyrosine kinase inhibitor) and BIM (protein kinase C inhibitor). Reporter gene assays demonstrated that albumin stimulates NF-kappaB mediated reporter gene activation in LLC-PK1 cells, which was partially inhibited by herbimycin A and BIM. Our data indicate, that albumin exposure induces a rapid increase in NF-kappaB protein activity in renal proximal tubule cells of different species via a tyrosine kinase- and protein kinase C-dependent pathway, at concentrations occurring during mild glomerular injury.

Topics: Albuminuria; Animals; Base Sequence; Benzoquinones; Cell Line; DNA; Enzyme Inhibitors; Gene Expression Regulation; Genes, Reporter; Humans; Indoles; Kidney Tubules, Proximal; Kinetics; Lactams, Macrocyclic; LLC-PK1 Cells; Maleimides; NF-kappa B; Opossums; Protein Kinase C; Protein-Tyrosine Kinases; Quinones; Rifabutin; Serum Albumin, Bovine; Species Specificity; Swine; Transcriptional Activation