Activation of NLR family, domain of pyrin containing 3 inflammasome by nitrous oxide through thioredoxin-interacting protein to induce nerve cell injury.

Abstract

Nitrous Oxide (N2O) has been shown to be neurotoxic, but its specific mechanism is still unclear. The purpose of this work is to probe into the impact of N2O on nerve cell injury through regulating thioredoxin-interacting protein (TXNIP)/the NOD-like receptor domain of pyrin containing 3 (NLRP3) pathway. The results indicated that, N2O exposure elevated TXNIP/NLRP3 expression in vivo and in vitro, led to declined learning and memory capabilities in mice, reduced apoptosis rate in hippocampal neuron and Nissl bodies, elevated inflammatory factors TNF-α, IL-1β and IL-6 levels, as well as cleaved caspase-3 and Bax expressions, and reduced Bcl-2 expression. Overexpressing TXNIP or NLRP3 further aggravated these injuries, but knocking down TXNIP or NLRP3 improved them. CO-IP indicated that TXNIP and NLRP3 can be combined, with interaction relationship. All in all, the results manifested that N2O is available to promote nerve cell inflammation and apoptosis through activating the TXNIP/NLRP3 pathway that can be used as a potential target for N2O-induced nerve damage in the future.