Immunohistochemical localization of glutamine transaminase K, a rat kidney cysteine conjugate beta-lyase, and the relationship to the segment specificity of cysteine conjugate nephrotoxicity.

Rat kidney glutamine transaminase K is a major rat kidney cysteine conjugate beta-lyase and is a key enzyme in the nephrotoxicity of some cysteine conjugates. However, it has not been demonstrated that the beta-lyase is present in the target cells. Furthermore, although all segments of the proximal tubule are affected by high doses of nephrotoxic cysteine conjugates, the S3 segment is the most sensitive. Because heterogeneous distribution of the beta-lyase could account for the enhanced sensitivity, antibody raised against rat kidney cysteine conjugate beta-lyase has been prepared and used to investigate the distribution of the enzyme in kidney and other tissues. The data show that the enzyme is highest in rat kidney, consistent with enzyme activity data. By immunohistochemical staining, no enzyme is present in the glomeruli or distal tubular elements of the kidney. The enzyme is present only in the target cells, the renal proximal tubular epithelium. However, the distribution of the beta-lyase within the proximal tubule is not consistent with the hypothesis that a higher concentration of the enzyme in the S3 segment accounts for the greater sensitivity of S3 to nephrotoxic cysteine conjugates compared to S1 and S2. Several alternative hypotheses are discussed.