Interplay of Nrf2 and BACH1 in inducing ferroportin expression and enhancing resistance of human macrophages towards ferroptosis.

ABSTRACT: Compared to cancer cells, macrophages are inert to lipid peroxidation-triggered, iron-dependent cell death known as ferroptosis. Mechanisms underlying macrophage resistance towards ferroptosis are largely obscure. Here, we show that human primary macrophages respond to RSL3, a ferroptosis-inducing inhibitor of glutathione peroxidase 4, by upregulating mRNA expression of the iron transporter ferroportin. RSL3 induces lipid peroxidation, and both, lipid peroxidation as well as ferroportin induction were attenuated by liproxstatin-1, an inhibitor of lipid peroxidation and ferroptosis blocker. At the same time, system x_c^- inhibitor erastin fails to elicit lipid peroxidation or ferroportin expression. Ferroportin induction in response to RSL3 demands nuclear accumulation o

SUBMITTER: Namgaladze D 

PROVIDER: S-EPMC9296510 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature