Nrf2 knockout altered brain iron deposition and mitigated age-related motor dysfunction in aging mice

Han, Kang Min; Jin, Xiaofang; Guo, Xiaomao; Cao, Guoli; Tian, Siyu; Song, Yiming; Zuo, Ya‐Gang; Yu, Peng; Gao, Guofen; Chang, Yan‐Zhong

doi:10.1016/j.freeradbiomed.2020.11.019

Cited by 52 publications

(37 citation statements)

References 47 publications

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“…Accumulating evidence has demonstrated that Nrf2 plays a vital role in ferroptosis by modulating iron homeostasis and oxidative stress. 40,41 Notably, several studies have revealed that the neuroprotective effect of KD is associated with Nrf2-mediated antioxidation, 11 but the underlying mechanism has not yet been fully elucidated. Sirt1 and Sirt3 are a class of NAD + -dependent deacetylases, and play a neuroprotective role by improving antioxidative stress, neuronal survival and synaptic plasticity.…”

Section: Papermentioning

confidence: 99%

A comparative study of the effect of a gentle ketogenic diet containing medium-chain or long-chain triglycerides on chronic sleep deprivation-induced cognitive deficiency

et al. 2022

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Section: Papermentioning

confidence: 99%

A comparative study of the effect of a gentle ketogenic diet containing medium-chain or long-chain triglycerides on chronic sleep deprivation-induced cognitive deficiency

et al. 2022

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“…NRF2 is an important antioxidant and anti-in ammatory regulator. It combines with downstream antioxidation response element (ARE) to control the transcription of GPX4, heme oxygenase-1 (HO-1), NADPH quinone oxidoreductase 1 (NQO1) and other genes 30) . NRF2 can also inhibit the degradation of IκB-α proteasome and the activation of NF-κB signaling pathway 31) .…”

Section: Discussionmentioning

confidence: 99%

Inhibition of USP14 suppresses ferroptosis and inflammation in LPS-induced goat mammary epithelial cells through ubiquitylating the IL-6 protein

Zhu¹,

Sui²,

SHI³

et al. 2022

Preprint

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Background Ferroptosis, a novel manner of cell death depended on iron ion, contributed to goat mammary epithelial cell dysfunction. Interleukin-6 (IL-6) is a major pro-inflammatory factor during many inflammation-related diseases including mastitis, and a quite recently identified ferroptosis inducer. This study aims to explore the role of IL-6 in the dysfunction of goat mammary epithelial cells (GMECs) and how the level of IL-6 was regulated. Methods Primary GMECs were isolated, cultured and treated with lipopolysaccharide (LPS) alone or together with Ferrostatin-1 (Fer-1), a well-known ferroptosis inhibitor. CCK-8 was used to detect cell viability, ELISA was used to detect TNF-α content, and the levels of ROS, GSH and MDA were analyzed with DCFDA-cell ROS detection kit, GSH assay kit and MDA assay kit, respectively. The iron ion level was measured with an iron assay kit. Results The expression level of IL-6 protein in GMECs was up-regulated in response to LPS treatment, and the secretion of TNF-α, the cell oxidative stress level and the Fe2+ ion content was robustly increased, which could be reversed by Fer-1 treatment. Knockdown of IL-6 decreased cell oxidative stress level and inhibited ferroptosis in LPS-treated GMECs. Further, ubiquitin experiment and co-immunoprecipitation assay showed that USP14 upregulated IL-6 protein expression by reducing the ubiquitination of IL-6, and overexpression of IL-6 reversed the inhibitory effect of USP14 shRNA on LPS-treated GMECs ferroptosis. The NRF2 inhibitor Brusatol reversed the inhibitory effect of IL-6 shRNA on LPS-treated ferroptosis. Conclusion IL-6 protein is deubiquitinated by USP14 and upregulated in LPS-treated GMECs, further promoting ferroptosis and inflammation through the NRF2 signaling pathway.

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“…Under oxidative stress condition, NRF2 detaches from Keap1 and translocates into the nucleus to modulate the cellular antioxidant response by increasing the expression of target genes involved in the metabolism of ROS, such as GPX4 and SLC7A11 (Qiang et al, 2020). In addition, the activation of NRF2 can also upregulate cellular NADPH, promote iron storage, and reduce cellular iron uptake (Kovac et al, 2015;Han et al, 2021). Therefore, the NRF2-Keap1 protein complex plays an important role in mediating lipid peroxidation and ferroptosis.…”

Section: Other Pathways and Processes Of Ferroptosismentioning

confidence: 99%

Ferroptosis and Its Role in Epilepsy

Cai

Yang

2021

Front. Cell. Neurosci.

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Epilepsy is one of the most common symptoms of many neurological disorders. The typical excessive, synchronous and aberrant firing of neurons originating from different cerebral areas cause spontaneous recurrent epileptic seizures. Prolonged epilepsy can lead to neuronal damage and cell death. The mechanisms underlying epileptic pathogenesis and neuronal death remain unclear. Ferroptosis is a newly defined form of regulated cell death that is characterized by the overload of intracellular iron ions, leading to the accumulation of lethal lipid-based reactive oxygen species (ROS). To date, studies have mainly focused on its role in tumors and various neurological disorders, including epilepsy. Current research shows that inhibition of ferroptosis is likely to be an effective therapeutic approach for epilepsy. In this review, we outline the pathogenesis of ferroptosis, regulatory mechanisms of ferroptosis, related regulatory molecules, and their effects on epilepsy, providing a new direction for discovering new therapeutic targets in epilepsy.

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Nrf2 knockout altered brain iron deposition and mitigated age-related motor dysfunction in aging mice

Cited by 52 publications

References 47 publications

A comparative study of the effect of a gentle ketogenic diet containing medium-chain or long-chain triglycerides on chronic sleep deprivation-induced cognitive deficiency

A comparative study of the effect of a gentle ketogenic diet containing medium-chain or long-chain triglycerides on chronic sleep deprivation-induced cognitive deficiency

Inhibition of USP14 suppresses ferroptosis and inflammation in LPS-induced goat mammary epithelial cells through ubiquitylating the IL-6 protein

Ferroptosis and Its Role in Epilepsy

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