{"title":"超越铁蛋白沉积诱导剂：麦拉宁能抑制营养匮乏诱导的椎间盘细胞死亡。","authors":"Jie Jin, Yu Chen, Ximiao Chen, Zengjie Zhang, Yaosen Wu, Naifeng Tian, Aimin Wu, Xiangyang Wang, Zhenxuan Shao, Yifei Zhou, Xiaolei Zhang, Yan Wu","doi":"10.1016/j.spinee.2024.10.018","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Erastin has been found to induce ferroptosis; however, whether erastin may have roles other than ferroptosis inducer in cells is unknown. Nutrient deficiency is one of the major causes of many diseases including intervertebral disc (IVD) degeneration.</p><p><strong>Purpose: </strong>The current study investigates the effect of erastin in nucleus pulposus cells under nutrient deprivation condition.</p><p><strong>Study design: </strong>Experiment in vitro and ex vivo.</p><p><strong>Methods: </strong>The effect of erastin on the cell survival of nucleus pulposus cells was evaluated in fetal bovine serum (FBS) and glucose deprivation condition. RSL3 and ferrostatin-1 were applied to illustrate whether the effect of erastin is ferroptosis dependent. The involvement of solute carrier family 7, membrane 11(SLC7A11), autophagy as well as mechanistic target of rapamycin kinase complex 1(mTORC1) and transcription factor EB (TFEB) were assessed to demonstrate the working mechanism of erastin.</p><p><strong>Results: </strong>Erastin may induce cell death at the concentration of ≥ 5μM; however, it may protect nucleus pulposus cells against nutrient deprivation induced cell death at lower concentration (0.25-1μM) and the effect of erastin is ferroptosis independent. The mechanism study showed that the effect of erastin may relate to its SCL7A11 regulation, as SCL7A11 knock-down may have the similar effect as erastin. Furthermore, it was also demonstrated that mTORC1-TFEB mediated autophagy was involved in protective effect of erastin.</p><p><strong>Conclusions: </strong>Low dose erastin may promote cell survival under nutrient deprivation condition, and its effect is ferroptosis independent; erastin may exert its protective effect through mTORC1-TFEB mediated autophagy regulation.</p><p><strong>Clinical significance: </strong>Nutrient deprivation is a major contributor to intervertebral disc degeneration. Our in vitro and ex vivo study showed that low dose of erastin may suppress nutrient deprivation induced cell death in IVD degeneration. Although it was not validated in vivo model due to lack of in vivo nutrient deprivation induced IVD degeneration model currently, this study may still provide a potential therapeutic option for IVD degeneration, which of cause need further validation.</p>","PeriodicalId":49484,"journal":{"name":"Spine Journal","volume":null,"pages":null},"PeriodicalIF":4.9000,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Beyond a ferroptosis inducer: erastin can suppress nutrient deprivation induced cell death in the intervertebral disc.\",\"authors\":\"Jie Jin, Yu Chen, Ximiao Chen, Zengjie Zhang, Yaosen Wu, Naifeng Tian, Aimin Wu, Xiangyang Wang, Zhenxuan Shao, Yifei Zhou, Xiaolei Zhang, Yan Wu\",\"doi\":\"10.1016/j.spinee.2024.10.018\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Erastin has been found to induce ferroptosis; however, whether erastin may have roles other than ferroptosis inducer in cells is unknown. Nutrient deficiency is one of the major causes of many diseases including intervertebral disc (IVD) degeneration.</p><p><strong>Purpose: </strong>The current study investigates the effect of erastin in nucleus pulposus cells under nutrient deprivation condition.</p><p><strong>Study design: </strong>Experiment in vitro and ex vivo.</p><p><strong>Methods: </strong>The effect of erastin on the cell survival of nucleus pulposus cells was evaluated in fetal bovine serum (FBS) and glucose deprivation condition. RSL3 and ferrostatin-1 were applied to illustrate whether the effect of erastin is ferroptosis dependent. The involvement of solute carrier family 7, membrane 11(SLC7A11), autophagy as well as mechanistic target of rapamycin kinase complex 1(mTORC1) and transcription factor EB (TFEB) were assessed to demonstrate the working mechanism of erastin.</p><p><strong>Results: </strong>Erastin may induce cell death at the concentration of ≥ 5μM; however, it may protect nucleus pulposus cells against nutrient deprivation induced cell death at lower concentration (0.25-1μM) and the effect of erastin is ferroptosis independent. The mechanism study showed that the effect of erastin may relate to its SCL7A11 regulation, as SCL7A11 knock-down may have the similar effect as erastin. Furthermore, it was also demonstrated that mTORC1-TFEB mediated autophagy was involved in protective effect of erastin.</p><p><strong>Conclusions: </strong>Low dose erastin may promote cell survival under nutrient deprivation condition, and its effect is ferroptosis independent; erastin may exert its protective effect through mTORC1-TFEB mediated autophagy regulation.</p><p><strong>Clinical significance: </strong>Nutrient deprivation is a major contributor to intervertebral disc degeneration. Our in vitro and ex vivo study showed that low dose of erastin may suppress nutrient deprivation induced cell death in IVD degeneration. Although it was not validated in vivo model due to lack of in vivo nutrient deprivation induced IVD degeneration model currently, this study may still provide a potential therapeutic option for IVD degeneration, which of cause need further validation.</p>\",\"PeriodicalId\":49484,\"journal\":{\"name\":\"Spine Journal\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.9000,\"publicationDate\":\"2024-11-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Spine Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.spinee.2024.10.018\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Spine Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.spinee.2024.10.018","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Beyond a ferroptosis inducer: erastin can suppress nutrient deprivation induced cell death in the intervertebral disc.
Background: Erastin has been found to induce ferroptosis; however, whether erastin may have roles other than ferroptosis inducer in cells is unknown. Nutrient deficiency is one of the major causes of many diseases including intervertebral disc (IVD) degeneration.
Purpose: The current study investigates the effect of erastin in nucleus pulposus cells under nutrient deprivation condition.
Study design: Experiment in vitro and ex vivo.
Methods: The effect of erastin on the cell survival of nucleus pulposus cells was evaluated in fetal bovine serum (FBS) and glucose deprivation condition. RSL3 and ferrostatin-1 were applied to illustrate whether the effect of erastin is ferroptosis dependent. The involvement of solute carrier family 7, membrane 11(SLC7A11), autophagy as well as mechanistic target of rapamycin kinase complex 1(mTORC1) and transcription factor EB (TFEB) were assessed to demonstrate the working mechanism of erastin.
Results: Erastin may induce cell death at the concentration of ≥ 5μM; however, it may protect nucleus pulposus cells against nutrient deprivation induced cell death at lower concentration (0.25-1μM) and the effect of erastin is ferroptosis independent. The mechanism study showed that the effect of erastin may relate to its SCL7A11 regulation, as SCL7A11 knock-down may have the similar effect as erastin. Furthermore, it was also demonstrated that mTORC1-TFEB mediated autophagy was involved in protective effect of erastin.
Conclusions: Low dose erastin may promote cell survival under nutrient deprivation condition, and its effect is ferroptosis independent; erastin may exert its protective effect through mTORC1-TFEB mediated autophagy regulation.
Clinical significance: Nutrient deprivation is a major contributor to intervertebral disc degeneration. Our in vitro and ex vivo study showed that low dose of erastin may suppress nutrient deprivation induced cell death in IVD degeneration. Although it was not validated in vivo model due to lack of in vivo nutrient deprivation induced IVD degeneration model currently, this study may still provide a potential therapeutic option for IVD degeneration, which of cause need further validation.
期刊介绍：
The Spine Journal, the official journal of the North American Spine Society, is an international and multidisciplinary journal that publishes original, peer-reviewed articles on research and treatment related to the spine and spine care, including basic science and clinical investigations. It is a condition of publication that manuscripts submitted to The Spine Journal have not been published, and will not be simultaneously submitted or published elsewhere. The Spine Journal also publishes major reviews of specific topics by acknowledged authorities, technical notes, teaching editorials, and other special features, Letters to the Editor-in-Chief are encouraged.
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