The mechanisms of ferroptosis and its role in atherosclerosis

Xu, Xi; Xu, Xiao-Dan; Ma, Meng-Qing; Liang, Yin; Cai, Yang-Bo; Zhu, Zi-Xian; Xu, Tao; Zhu, Lin; Ren, Kun

doi:10.1016/j.biopha.2023.116112

Cited by 13 publications

(2 citation statements)

References 102 publications

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“…Long-chain saturated fatty acids (SFA) are another target of lipid peroxidation. The peroxisomal enzyme fatty acyl-CoA reductase 1 reduces SFA to fatty alcohols, which are incorporated into the sn-1 position of PUFA-PLs, generating polyunsaturated ether phospholipids which can be hyperoxidized [14,76].…”

Section: Nuclear Translocation Of Nrf2 Depends On Fpr2 Stimulationmentioning

confidence: 99%

“…Therefore, the increased expression of SLC7A11/xCT on cancer cell surfaces enhances the uptake of cystine for intracellular GSH synthesis [11,12]. SLC7A11/xCT is primarily expressed in the brain [13] and plays functional roles in the pathophysiology of cancer and other diseases such as cardiovascular [14,15] and neurodegenerative [16] disease. Glioma cancer cells release high amounts of glutamate in the brain [17,18], suggesting the activation of the xCT system and the generation of a glutamate-rich microenvironment, which has a significant impact on the proliferation and matrix invasion of these cells [19].…”

Section: Introductionmentioning

confidence: 99%

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Formyl-Peptide Receptor 2 Signaling Modulates SLC7A11/xCT Expression and Activity in Tumor Cells

Pecchillo Cimmino,

Punziano,

Panico

et al. 2024

Antioxidants

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Cancer cells exhibit high levels of oxidative stress and consequently require a high amount of cysteine for glutathione synthesis. Solute Carrier Family 7 Member 11 (SLC7A11), or xCT, mediates the cellular uptake of cystine in exchange for intracellular glutamate; imported extracellular cystine is reduced to cysteine in the cytosol through a NADPH-consuming reduction reaction. SLC7A11/xCT expression is under the control of stress-inducing conditions and of several transcription factors, such as NRF2 and ATF4. Formyl-peptide receptor 2 (FPR2) belongs to the FPR family, which transduces chemotactic signals mediating either inflammatory or anti-inflammatory responses according to the nature of its ligands and/or FPR2 binding with other FPR isoforms. The repertoire of FPR2 agonists with anti-inflammatory activities comprises WKYMVm peptide and Annexin A1 (ANXA1), and the downstream effects of the intracellular signaling cascades triggered by FPR2 include NADPH oxidase (NOX)-dependent generation of reactive oxygen species. Herein, we demonstrate that stimulation of CaLu-6 cells with either WKYMVm or ANXA1: (i) induces the redox-regulated activation of SLC7A11/xCT; (ii) promotes the synthesis of glutathione; (iii) prevents lipid peroxidation; and (iv) favors NRF2 nuclear translocation and activation. In conclusion, our overall results demonstrate that FPR2 agonists and NOX modulate SLC7A11/xCT expression and activity, thereby identifying a novel regulative pathway of the cystine/glutamate antiport that represents a new potential therapeutical target for the treatment of human cancers.

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Section: Nuclear Translocation Of Nrf2 Depends On Fpr2 Stimulationmentioning

confidence: 99%