Activation of antioxidant defense during dehydration stress in the African clawed frog

The glutathione S-transferase (GST) and aldo-keto reductase (AKR) families of proteins are major groups of detoxifying enzymes that are known to be regulated by the NF-E2 related factor 2 (Nrf2) transcription factor via the antioxidant response element that is present in the promoter regions of GST and AKR genes. Expression of Nrf2, GST and AKR proteins was analyzed in the African clawed frog, Xenopus laevis, focusing on their responses to dehydration stress. Dehydration/rehydration cycles can generate oxidative stress and this could be ameliorated by enhancing antioxidant defenses. Dehydration to 28% of total body water lost triggered organ-specific changes in nrf2 mRNA expression (a 2-fold increase in liver), total Nrf2 protein (2-4-fold elevation in lung, heart, skin and liver), and a 4.3-fold increase in the content of Nrf2 in the nucleus in muscle. Protein levels of six GST and three AKR family members were assessed and showed organ-specific patterns of expression during dehydration. In particular, GSTP1 was strongly induced in liver, heart and skin, levels rising by 9-, 2.6- and 1.7-fold, respectively, whereas GSTM1 and M3 rose in skeletal muscle, kidney and skin. Selective expression of GSTK1, A3 and T1 also occurred. Dehydration also stimulated organ-specific increases in the levels of AKR family members (AKR1B4, AKR1A3, AFAR1) by 1.5-2-fold. The results show that metabolic responses to dehydration include activation of the Nrf2 transcription factor and selective up-regulation of genes under Nrf2 control.