Abstract
Ferroptosis, a form of programmed cell death triggered by iron-dependent lipid peroxidation, has been associated with various diseases. Organisms possess defense mechanisms against oxidative stress, including antioxidant enzymes like glutathione peroxidase (GPx) and thioredoxin reductase, which contain selenocysteine in their active sites. GPx4 plays a crucial role in reducing lipid peroxides and is directly involved in ferroptosis.
Selenoprotein P (SeP) is essential for delivering selenium to selenium-containing proteins. It is primarily mainly produced in the liver, secreted into the bloodstream, and facilitates selenium transport throughout the body. Recently we found SeP regulates cellular selenium levels, impacting ferroptosis sensitivity via GPx4 expression. In liver cells, inhibiting SeP secretion increases intracellular selenium and GPx4 expression, thus protecting against ferroptosis. Conversely, glioblastoma cell lines experience reduced intracellular GPx4 and heightened ferroptosis susceptibility with SeP inhibition. These findings indicated that SeP not only transports selenium to other organs but also plays a crucial role in selenium circulation within tissues through autocrine/paracrine pathways.
In this presentation, we outline the selenium cycle system managed by SeP, correlating it with intracellular antioxidant capacity and ferroptosis resistance. We also explore cancer progression due to selenium imbalance, incorporating patient tissue analyses and computational insights, and suggest SeP-focused treatment strategies.
