Thioredoxin reductase inhibition elicits Nrf2-mediated responses in Clara cells: implications for oxidant-induced lung injury.

ABSTRACT:

Aims

Pulmonary oxygen toxicity contributes to lung injury in newborn and adult humans. We previously reported that thioredoxin reductase (TrxR1) inhibition with aurothioglucose (ATG) attenuates hyperoxic lung injury in adult mice. The present studies tested the hypothesis that TrxR1 inhibition protects against the effects of hyperoxia via nuclear factor E2-related factor 2 (Nrf2)-dependent mechanisms.

Results

Both pharmacologic and siRNA-mediated TrxR1 inhibition induced robust Nrf2 responses in murine-transformed Clara cells (mtCC). While TrxR1 inhibition did not alter the susceptibility of cells to the effects of hyperoxia, glutathione (GSH) depletion after TrxR1 inhibition markedly enhanced the hyperoxic susceptibility of cultured mtCCs. Finally, in vivo data revealed dos

SUBMITTER: Locy ML 

PROVIDER: S-EPMC3437047 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature