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NSC-34 motor neuron-like cells are sensitized to ferroptosis upon differentiation.

ABSTRACT: Ferroptosis is a form of regulated cell death that is driven by lethal accumulation of lipid peroxides upon inhibition of glutathione peroxidase 4 (GPx4). Deletion of the Gpx4 gene in mice revealed that neurons are sensitive to ferroptosis in vivo. However, few studies have been conducted on ferroptosis regulation in neurons. Here, we report that cells of a motor neuron-like cell line, NSC-34, became more sensitive to ferroptosis upon differentiation into a more motor neuron-like condition. We identified three factors that influence ferroptosis sensitivity under differentiation conditions: low serum antioxidants, decreased GPx4 protein amount, and inhibition of the transsulfuration pathway. Our results support the hypothesis that neurons, especially motor neurons, are sensitive to ferroptosis, and suggest that ferroptosis in a neuronal context should be investigated further to develop strategies for neuroprotection.

SUBMITTER: Martinez AM

PROVIDER: S-EPMC6443867 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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NSC-34 motor neuron-like cells are sensitized to ferroptosis upon differentiation.

Martinez Alejandra M AM Mirkovic Jovan J Stanisz Zofia A ZA Patwari Fahmida S FS Yang Wan Seok WS

FEBS open bio 20190223 4

Ferroptosis is a form of regulated cell death that is driven by lethal accumulation of lipid peroxides upon inhibition of glutathione peroxidase 4 (GPx4). Deletion of the <i>Gpx4</i> gene in mice revealed that neurons are sensitive to ferroptosis <i>in vivo</i>. However, few studies have been conducted on ferroptosis regulation in neurons. Here, we report that cells of a motor neuron-like cell line, NSC-34, became more sensitive to ferroptosis upon differentiation into a more motor neuron-like c ...[more]

PMID: 30984534

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