Selenite suppresses hydrogen peroxide-induced cell apoptosis through inhibition of ASK1/JNK and activation of PI3-K/Akt pathways

The relationship between selenium and signal molecules has not been well el ucidated. It was found that physiological concentration of selenite, <3 <mu >M, reduced ASK1 activity and induced PI3-kinase (PI3-K)/Akt pathways in HT 1080 cells. Duration of these signal molecules by selenite was much longer than that by growth factors and other stresses. The longer duration time of these signal molecules may be important to maintain normal functions again st stresses. Selenite increased cell proliferation through up-regulation of Bcl-2 expression, mitochondrial membrane potential, adenosine triphosphate (ATP) generation, and glucose uptake mediated by PI3-K pathway. High conce ntration of H2O2 increased an apoptotic signal molecule, ASK1, which result ed in Bcl-2 down-regulation, membrane potential disruption, decreased ATP a nd glucose uptake, and activation of caspases. However, an antiapoptotic si gnal molecule, Akt, was activated also by H2O2, but duration of its activat ion was much shorter. Selenite blocked apoptosis induced by H2O2, which was related to blocking ASK1 and further stimulating PI3-kinase/Akt activities . Selenite blocked mitochondrial membrane potential disruption by 400 muM H 2O2. Selenite also blocked caspase-9 and -3 activities and apoptosis induce d by 500 muM H2O2, even after mitochondrial membrane potential disruption. These observations demonstrate that selenite increases cell proliferation a nd maintains cell survival by activating the antiapoptotic signal and block ing the apoptotic signal.