Highlights d 3F3-FMA is identified in a screen as a selective ferroptosisimmunostaining reagent d The antigen of 3F3-FMA is identified as the transferrin receptor 1 protein (TfR1) d Anti-TfR1 antibodies can detect ferroptosis by immunofluorescence and flow cytometry d Anti-TfR1 and anti-MDA antibodies detect ferroptosis in xenograft cancer models
The regenerative capacity of skeletal muscle declines with age. Previous studies suggest that this process can be reversed by exposure to young circulation, but systemic age-specific factors responsible for this phenomenon are largely unknown. Here we report that oxytocin- a hormone best known for its role in lactation, parturition, and social behaviors - is required for proper muscle tissue regeneration and homeostasis, and that plasma levels of oxytocin decline with age. Inhibition of oxytocin signaling in young animals reduces muscle regeneration, whereas systemic administration of oxytocin rapidly improves muscle regeneration by enhancing aged muscle stem cell activation/proliferation throughactivation of the MAPK/ERK signalling pathway. We further show that the genetic lack of oxytocin does not cause a developmental defect in muscle, but instead leads to premature sarcopenia. Considering that oxytocin is an FDA approved drug, this work reveals a potential novel and safe way to combat or prevent skeletal muscle aging.
Although
radiation is widely used to treat cancers, resistance
mechanisms often develop and involve activation of DNA repair and
inhibition of apoptosis. Therefore, compounds that sensitize cancer
cells to radiation via alternative cell death pathways are valuable.
We report here that ferroptosis, a form of nonapoptotic cell death
driven by lipid peroxidation, is partly responsible for radiation-induced
cancer cell death. Moreover, we found that small molecules activating
ferroptosis through system xc
– inhibition
or GPX4 inhibition synergize with radiation to induce ferroptosis
in several cancer types by enhancing cytoplasmic lipid peroxidation
but not increasing DNA damage or caspase activation. Ferroptosis inducers
synergized with cytoplasmic irradiation, but not nuclear irradiation.
Finally, administration of ferroptosis inducers enhanced the antitumor
effect of radiation in a murine xenograft model and in human patient-derived
models of lung adenocarcinoma and glioma. These results suggest that
ferroptosis inducers may be effective radiosensitizers that can expand
the efficacy and range of indications for radiation therapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.