Cross-Linking of Thioredoxin Reductase by the Sulfur Mustard Analogue Mechlorethamine (Methylbis(2-chloroethyl)amine) in Human Lung Epithelial Cells and Rat Lung: Selective Inhibition of Disulfide Reduction but Not Redox Cycling

Oxidative stress plays a key role in mechlorethamine (methylbis(2-chloroethyl)amine, HN2) toxicity. The thioredoxin system, consisting of thioredoxin reductase (TrxR), thioredoxin, and NADPH, is important in redox regulation and protection against oxidative stress. HN2 contains two electrophilic side chains that can react with nucleophilic sites in proteins, leading to changes in their structure and function. We report that HN2 inhibits the...