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 S1S-Antilles, NY1DD, and control mice were measured by ELISA, which revealed that the serum of S1S-Antilles mice, relative to controls, had elevated levels of murine glutathione S-transferase A1-1 (P 5 0.005) as did NY1DD mice (P 5 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 S1S-Antilles mice relative to controls (P 5 0.000006, P 5 0.0003, and P 5 0.029, respectively). Urine murine glutathione S-transferase A1-1 of S1S-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. V

Magnesium homeostasis in deoxygenated sickle erythrocytes is modulated by endothelin‐1 via Na + /Mg 2+ exchange

“…(A) Na + ‐dependent Mg 2+ efflux was measured in red cells of mouse hemoglobinopathy models as described in Methods . These included Wild‐type mice (WT: C57Bl/6j), SAD, 45 BERK 42 and NY1DD 44 mouse models of sickle cell disease, and human HbC‐expressing mice. 43 Values represent means ± SEM for ≥3 quadruplicate experiments.…”

“…BERK and BERK‐trait mice (homozygous α knockout, heterozygous β knockout) of both sexes were studied at ages of 3–6 months. HbC (Hba + /Hba + /Hbb 0 /Hbb 0 ) transgenic mice 43 and NY1DD transgenic mice 44 were provided by Dr. Mary Fabry (Albert Einstein College of Medicine, Bronx, NY, USA). Male and female mice between 8 and 16 weeks of age were studied.…”