SCP2 mediates the transport of lipid hydroperoxides to mitochondria in chondrocyte ferroptosis

Dai, Ting; Xue, Xiang; Huang, Jin; Yang, Zhenyu; Xu, Pengfei; Wang, Min; Xu, Wuyan; Feng, Zhencheng; Zhu, Weicong; Xu, Yangyang; Chen, Junyan; Li, Siming; Meng, Qingqi

doi:10.1038/s41420-023-01522-x

Cited by 10 publications

(4 citation statements)

References 42 publications

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“…Mitochondria are the main energy supply organs of ATP. Sterol carrier protein 2-mediated trafficking of peroxidized lipids to mitochondria promotes GPX4 depletion-induced ferroptosis, supporting a role for mitochondria in ferroptosis [ 54 ]. Next, hippocampal tissues from mice were subjected to transmission electron microscopy to elucidate the mitochondrial membrane state after P2RX7 inhibition.…”

Section: Resultsmentioning

confidence: 99%

The microRNA-211-5p/P2RX7/ERK/GPX4 axis regulates epilepsy-associated neuronal ferroptosis and oxidative stress

Li,

Quan,

et al. 2024

J Neuroinflammation

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Ferroptosis is an iron-dependent cell death mechanism involving the accumulation of lipid peroxides. As a critical regulator, glutathione peroxidase 4 (GPX4) has been demonstrated to be downregulated in epilepsy. However, the mechanism of ferroptosis in epilepsy remains unclear. In this study, bioinformatics analysis, analysis of epilepsy patient blood samples and cell and mouse experiments revealed strong associations among epilepsy, ferroptosis, microRNA-211-5p and purinergic receptor P2X 7 (P2RX7). P2RX7 is a nonselective ligand-gated homotrimeric cation channel, and its activation mainly increases neuronal activity during epileptic seizures. In our study, the upregulation of P2RX7 in epilepsy was attributed to the downregulation of microRNA (miR)-211-5p. Furthermore, P2RX7 has been found to regulate GPX4/HO-1 by alleviating lipid peroxidation induced by suppression of the MAPK/ERK signaling pathway in murine models. The dynamic decrease in miR-211-5p expression induces hypersynchronization and both nonconvulsive and convulsive seizures, and forebrain miR-211-5p suppression exacerbates long-lasting pentylenetetrazole-induced seizures. Additionally, in this study, induction of miR-211-5p expression or genetic-silencing of P2RX7 significantly reduced the seizure score and duration in murine models through the abovementioned pathways. These results suggest that the miR-211-5p/P2RX7 axis is a novel target for suppressing both ferroptosis and epilepsy.

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Section: Resultsmentioning

confidence: 99%

The microRNA-211-5p/P2RX7/ERK/GPX4 axis regulates epilepsy-associated neuronal ferroptosis and oxidative stress

Li,

Quan,

et al. 2024

J Neuroinflammation

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“…[58] Another study demonstrated that sterol carrier protein 2 (SCP2) facilitated the transport of cytoplasmic LPO to mitochondria, contributing to the spread of intracellular LPO and accelerating chondrocyte ferroptosis. [59] Bioinformatics analysis and machine learning techniques identified several ferroptosis-related genes involved in OA. The genes ATF3, IL6, CDKN1A, IL1B, EGR1, CD44, AQP8, BRD7, IFNA4, and ARHGEF26-AS1 have been identified as potential target genes for reducing iron overload during OA treatment.…”

Section: Iron Metabolism and Oamentioning

confidence: 99%

Section: Iron Metabolism and Arthritismentioning

confidence: 99%

“…Some key ferroptosis-related targets, such as DMT1, transient receptor potential vanilloid 1 (TRPV1), staphylococcal nuclease domain containing 1 (SND1), Piezo1, SLC3A2, GPX4, NCOA4, excitatory amino acid transporter 1 (EAAT1), SCP2, and FOXO3, are potential new drug research targets for treating OA. [ 54 59 64 65 66 67 68 69 70 71 ] Recent research has shown that various natural medicinal factors (such as stigmasterol, D-mannose, naringenin, astaxanthin, metformin, theaflavin-3,3′-digallate, biochanin A, sarsasapogenin, kukoamine A, cardamonin, calcipotriol, brevilin A, and baicalein) have therapeutic benefits in combating the occurrence of OA by inhibiting the ferroptosis pathway and have multiple targets and pathways, providing new ideas and methods for the treatment of OA. [ 72 73 74 75 76 77 78 79 80 81 82 83 84 85 ] Some chemical reagents, such as DFO and the calcium chelator BAPTA-AM, are potential therapeutic drug components.…”

Section: Iron Metabolism and Arthritismentioning

confidence: 99%

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Iron metabolism and arthritis: Exploring connections and therapeutic avenues

Zhuo,

Xiao,

Tang

et al. 2024

Chinese Medical Journal

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Iron is indispensable for the viablility of nearly all living organisms, and it is imperative for cells, tissues, and organisms to acquire this essential metal sufficiently and maintain its metabolic stability for survival. Disruption of iron homeostasis can lead to the development of various diseases. There is a robust connection between iron metabolism and infection, immunity, inflammation, and aging, suggesting that disorders in iron metabolism may contribute to the pathogenesis of arthritis. Numerous studies have focused on the significant role of iron metabolism in the development of arthritis and its potential for targeted drug therapy. Targeting iron metabolism offers a promising approach for individualized treatment of arthritis. Therefore, this review aimed to investigate the mechanisms by which the body maintains iron metabolism and the impacts of iron and iron metabolism disorders on arthritis. Furthermore, this review aimed to identify potential therapeutic targets and active substances related to iron metabolism, which could provide promising research directions in this field.

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Natural Products in the Prevention of Degenerative Bone and Joint Diseases: Mechanisms Based on the Regulation of Ferroptosis

Gao,

Lv,

et al. 2024

Phytotherapy Research

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Degenerative bone and joint diseases (DBJDs), characterized by osteoporosis, osteoarthritis, and chronic inflammation of surrounding soft tissues, are systemic conditions primarily affecting the skeletal system. Ferroptosis, a programmed cell death pathway distinct from apoptosis, autophagy, and necroptosis. Accumulating evidence suggests that ferroptosis is intricately linked to the pathogenesis of DBJDs, and targeting its regulation could be beneficial in managing these conditions. Natural products, known for their anti‐inflammatory and antioxidant properties, have shown unique advantages in preventing DBJDs, potentially through modulating ferroptosis. This article provides an overview of the latest research on ferroptosis, with a focus on its role in the pathogenesis of DBJDs and the therapeutic potential of natural products targeting this cell death pathway, offering novel insights for the prevention and treatment of DBJDs.

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SCP2 mediates the transport of lipid hydroperoxides to mitochondria in chondrocyte ferroptosis

Cited by 10 publications

References 42 publications

The microRNA-211-5p/P2RX7/ERK/GPX4 axis regulates epilepsy-associated neuronal ferroptosis and oxidative stress

The microRNA-211-5p/P2RX7/ERK/GPX4 axis regulates epilepsy-associated neuronal ferroptosis and oxidative stress

Iron metabolism and arthritis: Exploring connections and therapeutic avenues

Natural Products in the Prevention of Degenerative Bone and Joint Diseases: Mechanisms Based on the Regulation of Ferroptosis

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