title: Murine glutathione S-transferase A1-1 in sickle transgenic mice.
abstract: 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.
authors.affiliation: Division of Hematology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. yginzbur@montefiore.org
authors.forename: Yelena Z
authors.initials: YZ
authors.lastname: Ginzburg
authors.forename: John H
authors.initials: JH
authors.lastname: Andorfer
authors.forename: Anne C
authors.initials: AC
authors.lastname: Rybicki
authors.forename: Mary E
authors.initials: ME
authors.lastname: Fabry
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Nagel
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000755:Anemia, Sickle Cell / Q000150:complications / Q000201:enzymology* / Q000235:genetics; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004790:Enzyme Induction; D005260:Female; D020869:Gene Expression Profiling; D005914:Globins / Q000235:genetics*; D005982:Glutathione Transferase / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics / Q000652:urine; D006451:Hemoglobin, Sickle / Q000235:genetics*; D006504:Hepatic Veno-Occlusive Disease / Q000201:enzymology* / Q000209:etiology; D006801:Humans; D000860:Hypoxia / Q000201:enzymology; D007527:Isoenzymes / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics / Q000652:urine; D007674:Kidney Diseases / Q000201:enzymology* / Q000209:etiology; D007684:Kidney Tubules / Q000201:enzymology / Q000473:pathology; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: D006451:Hemoglobin, Sickle; D007527:Isoenzymes; D005914:Globins; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase