Murine glutathione S-transferase A1-1 in sickle transgenic mice

Patients with sickle cell anemia exhibit mild to moderate renal and liver damage. Glutathione S-transferase A1-1 is produced during kidney and liver damage. We hypothesized that cellular damage in sickle transgenic mice would lead to increased serum and urine murine glutathione S-transferase A1-1 levels. Levels of murine glutathione S-transferase A1-1 in the serum and urine of S+S-Antilles, NY1DD, and control mice were measured by ELISA, which revealed that the serum of S+S-Antilles mice, relative to controls, had elevated levels of murine glutathione S-transferase A1-1 (P = 0.005) as did NY1DD mice (P = 0.02, baseline vs. 2-day hypoxia). Serum liver enzymes, such as aspartate amino transferase and alanine amino transferase, as well as lactate dehydrogenase were increased in S+S-Antilles mice relative to controls (P = 0.000006, P = 0.0003, and P = 0.029, respectively). Urine murine glutathione S-transferase A1-1 of S+S-Antilles mice, as well as NY1DD mice under hypoxic stress, was not significantly different from controls. Murine glutathione S-transferase class-mu was measured by ELISA in the urine of sickle transgenic mice and control mice to define the location of tubular damage at the proximal convoluted tubule; murine Glutathione S-transferase class-mu was below the limit of detection. These findings suggest that elevated levels of murine glutathione S-transferase A1-1 in the serum reflect release during liver damage and that proximal tubular damage does not lead to appreciable urinary murine glutathione S-transferase A1-1.