Effects of lead on the kidney: roles of high-affinity lead-binding proteins.
Lead-induced nephropathy produces both tubular and interstitial manifestations of cell injury, but the pathophysiology of these lesions is not completely understood. Delineation of the molecular factors underlying renal handling of lead is one of central importance in understanding the mechanisms of renal cell injury from this agent. Recent studies from this laboratory have identified several distinct high-affinity lead-binding proteins (PbBP) from rat kidney and brain that appear to play critical roles in the intracellular bioavailability of lead to several essential cellular processes in these target tissues at low dose levels. The PbBP from rat kidney has been shown to be a specific cleavage product of alpha 2-microglobulin, which is a member of the retinol-binding protein superfamily. Recent preliminary Western blot and immunohistochemical studies have shown that a polyclonal antibody to the renal PbBP does not recognize the brain PbBP, which appears to be a chemically similar, but distinct molecule. These studies have also shown that the renal PbBP is selectively localized in only certain nephrons and only specific segments of the renal proximal tubule. The striking nephror and cell-type specificity of the localization reaction could result from physiological differences in nephron functional activity or selective molecular uptake mechanisms/metabolism differences that act to define target cell populations in the kidney. In addition, other preliminary studies have shown that short-term, high-dose lead exposure produces increased excretion of this protein into the urine with concomitant decreases in renal concentrations.
Fowler
B A
BA
Program in Toxicology, University of Maryland, Baltimore, MD 21201.
DuVal
G
G
D000510:Alpha-Globulins / Q000032:analysis; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000502:physiology*; D005260:Female; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D007668:Kidney / Q000737:chemistry*; D007674:Kidney Diseases / Q000139:chemically induced*; D007854:Lead / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D011485:Protein Binding; D051381:Rats
D000510:Alpha-Globulins; D002352:Carrier Proteins; C025500:alpha(2)-microglobulin; C055217:lead-binding proteins; D007854:Lead