Immunohistochemical Localization of Thioredoxin and Glutaredoxin in Mouse Embryos and Fetuses

Abstract

Although oxygen is essential for promoting energy metabolism and for enhancing cell proliferation, early mouse embryos are very sensitive to high oxygen concentration. Because the tissue-specificity and sequential changes of the expression of antioxidative enzymes in rodent embryos have not been investigated systematically, we examined the ontogenesis of thioredoxin (TRX) and glutaredoxin (GRX) in mouse embryos and fetuses by using immunohistochemical methods. These compounds were found to be localized in most tissues examined, with some tissue specificity and temporal sequence. In many tissues, both TRX and GRX began to be expressed at embryonic day 11 (E11) or E13 and appeared to increase later in development, but the heart and great vessels of E8.5 embryos were already positive for their immunoreactivity. The stage at which the antioxidative enzymes begin to be expressed seems to coincide with the stage at which rodent embryos acquire the capacity of aerobic energy metabolism. Although TRX and GRX were co-localized in many tissues and showed similar sequential changes of expression, their expression patterns were different in the fetal cartilage, suggesting that they may play different roles in endochondral ossification. Their immunoreactivity was not homogeneous in the liver and the epithelium of uriniferous tubules, probably because their expression is associated with the proliferating and metabolic activities of the cell, as suggested by previous investigators. These results suggest that TRX and GRX play some tissue-specific roles in mammalian morphogenesis as well as general roles as antioxidant enzymes.

Glutaredoxin regulates vascular development by reversible glutathionylation of sirtuin 1

“…Because GSH levels have been described as important for endothelial cell differentiation (39), and altering these levels significantly influences tumor angiogenesis (40), investigating the role of Grx2-regulated SIRT1 glutathionylation in malignant angiogenesis might reveal novel therapeutic strategies. Our study extends a previous descriptive report on Grx immunoreactivity observed in early mouse development during the onset of vasculogenesis (41). We demonstrated that redox signaling based on Grx-dependent reversible S-glutathionylation is not only important during pathology of the cardiovascular system but also for its development.…”

Transgenic mice overproducing human thioredoxin-1, an antioxidative and anti-apoptotic protein, prevents diabetic embryopathy

“…More recently, Kobayashi et al showed that TRX-Tg embryos were significantly more resistant to the teratogenic effects of hyperoxia than WT embryos [39]. TRX protein production begins in embryonic tissues from day 8 to 10 gestation, which is the time that organogenesis commences and the time that metabolic state of embryos becomes active [40]. Thus, the TRX protein may contribute to the regulation or the modulation of oxidative stress in embryos.…”

Thioredoxin Reductase Inhibition Elicits Nrf2-Mediated Responses in Clara Cells: Implications for Oxidant-Induced Lung Injury

“…In fetal and adult murine lungs and in adult human lungs, Trx1 and TrxR1 are predominantly expressed in ciliated and non-ciliated (Clara) conducting airway epithelial cells (10,13,23,36).…”