Thioredoxin reductase 1 (TrxR1) (TrxR1)

Thioredoxin reductase 1 (TrxR1) is a critical selenium-containing homodimeric enzyme that maintains cellular redox homeostasis by reducing thioredoxin (Trx) using NADPH as an electron donor (UniProt P31350). This enzyme system is essential for various cellular processes, including DNA synthesis via ribonucleotide reductase, antioxidant defense, and the regulation of redox-sensitive transcription factors and apoptotic pathways. In many malignancies, TrxR1 is significantly overexpressed to support rapid tumor cell proliferation and provide resistance against oxidative stress induced by chemotherapy and radiation (PubMed: 24631455). Motexafin gadolinium (MGd) is a synthetic texaphyrin that specifically targets TrxR1, acting as a redox-active agent that disrupts the thioredoxin system. By inhibiting TrxR1 or acting as a subversive substrate, MGd promotes the accumulation of reactive oxygen species (ROS), leading to severe oxidative stress and programmed cell death, particularly in highly metabolic cancer cells (Magda et al., 2002).

Other names

TXNRD1TR1TRXR1Thioredoxin-disulfide reductaseCytosolic thioredoxin reductase

Motexafin gadolinium acts as a redox-active agent that serves as a subversive substrate for thioredoxin reductase, leading to the depletion of NADPH, the accumulation of reactive oxygen species (ROS), and the inhibition of thioredoxin reduction, which collectively induce oxidative stress and apoptosis in cancer cells (Magda et al., 2002; Hashemy et al., 2006).