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

• Published in: American journal of hematology 2007-10, Vol.82 (10), p.911-915
• Main Authors: Ginzburg, Yelena Z., Andorfer, John H., Rybicki, Anne C., Fabry, Mary E., Nagel, Ronald L.
• Format: Article
• Language: English
• Subjects: Alanine Transaminase - blood; Anemia, Sickle Cell - complications; Anemia, Sickle Cell - enzymology; Anemia, Sickle Cell - genetics; Animals; Aspartate Aminotransferases - blood; Enzyme Induction; Female; Gene Expression Profiling; Globins - genetics; Glutathione Transferase - biosynthesis; Glutathione Transferase - blood; Glutathione Transferase - genetics; Glutathione Transferase - urine; Hemoglobin, Sickle - genetics; Hepatic Veno-Occlusive Disease - enzymology; Hepatic Veno-Occlusive Disease - etiology; Humans; Hypoxia - enzymology; Isoenzymes - biosynthesis; Isoenzymes - blood; Isoenzymes - genetics; Isoenzymes - urine; Kidney Diseases - enzymology; Kidney Diseases - etiology; Kidney Tubules - enzymology; Kidney Tubules - pathology; Liver - enzymology; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic
• ISSN: 0361-8609; 1096-8652
• DOI: 10.1002/ajh.20941

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. Am. J. Hematol. 82:911–915, 2007. © 2007 Wiley‐Liss, Inc.