Considerations for Using Neuroblastoma Cell Lines to Examine the Roles of Iron and Ferroptosis in Neurodegeneration

神经退行性变 神经母细胞瘤 神经科学 生物 癌症研究 医学 细胞培养 遗传学 病理 疾病
作者
Cameron J. Cardona,Yoo Kim,Winyoo Chowanadisai,McKale R. Montgomery
出处
期刊:Cells [Multidisciplinary Digital Publishing Institute]
卷期号:13 (18): 1541-1541
标识
DOI:10.3390/cells13181541
摘要

Ferroptosis is an iron-dependent form of programmed cell death that is influenced by biological processes such as iron metabolism and senescence. As brain iron levels increase with aging, ferroptosis is also implicated in the development of age-related pathologic conditions such as Alzheimer’s disease (AD) and related dementias (ADRD). Indeed, inhibitors of ferroptosis have been shown to be protective in models of degenerative brain disorders like AD/ADRD. Given the inaccessibility of the living human brain for metabolic studies, the goal of this work was to characterize an in vitro model for understanding how aging and iron availability influence neuronal iron metabolism and ferroptosis. First, the human (SH-SY5Y) and mouse (Neuro-2a) neuroblastoma lines were terminally differentiated into mature neurons by culturing in all-trans-retinoic acid for at least 72 h. Despite demonstrating all signs of neuronal differentiation and maturation, including increased expression of the iron storage protein ferritin, we discovered that differentiation conferred ferroptosis resistance in both cell lines. Gene expression data indicates differentiated neurons increase their capacity to protect against iron-mediated oxidative damage by augmenting cystine import, and subsequently increasing intracellular cysteine levels, to promote glutathione production and glutathione peroxidase activity (GPX). In support of this hypothesis, we found that culturing differentiated neurons in cysteine-depleted media sensitized them to GPX4 inhibition, and that these effects are mitigated by cystine supplementation. Such findings are important as they provide guidance for the use of in vitro experimental models to investigate the role of ferroptosis in neurodegeneration in pathologies such as ADRD.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
1秒前
心神依然完成签到,获得积分20
3秒前
xiaokezhang发布了新的文献求助10
6秒前
小魏完成签到,获得积分10
10秒前
李子敬完成签到,获得积分10
10秒前
SciGPT应助nanana采纳,获得10
10秒前
15秒前
天天快乐应助科研通管家采纳,获得10
15秒前
爆米花应助科研通管家采纳,获得10
15秒前
15秒前
ZZ完成签到,获得积分10
16秒前
举栗子完成签到 ,获得积分10
16秒前
今后应助Apple采纳,获得10
19秒前
迷人世开完成签到,获得积分0
21秒前
22秒前
jiajiajai完成签到,获得积分10
23秒前
ccqqww完成签到,获得积分10
23秒前
24秒前
Apple应助文件撤销了驳回
25秒前
1793275356关注了科研通微信公众号
26秒前
carbonhan完成签到,获得积分10
28秒前
ccqqww发布了新的文献求助10
28秒前
冰冰Y哦呀完成签到,获得积分10
29秒前
自然白安完成签到 ,获得积分10
31秒前
漂亮夏兰完成签到 ,获得积分10
37秒前
在水一方应助冰冰Y哦呀采纳,获得10
37秒前
倒数第二完成签到,获得积分10
39秒前
40秒前
44秒前
科研通AI2S应助ling采纳,获得10
44秒前
多情道之完成签到 ,获得积分10
45秒前
桐桐完成签到,获得积分0
46秒前
飘逸丸子完成签到,获得积分10
49秒前
阳光的静白完成签到,获得积分10
53秒前
CTL完成签到,获得积分10
54秒前
小二郎应助眼睛大向薇采纳,获得10
55秒前
安诺完成签到,获得积分10
56秒前
阿南完成签到 ,获得积分10
57秒前
小余同学发布了新的文献求助10
1分钟前
歪比巴卜发布了新的文献求助20
1分钟前
高分求助中
Les Mantodea de Guyane Insecta, Polyneoptera 2500
Technologies supporting mass customization of apparel: A pilot project 450
A Field Guide to the Amphibians and Reptiles of Madagascar - Frank Glaw and Miguel Vences - 3rd Edition 400
Brain and Heart The Triumphs and Struggles of a Pediatric Neurosurgeon 400
Cybersecurity Blueprint – Transitioning to Tech 400
Mixing the elements of mass customisation 400
Периодизация спортивной тренировки. Общая теория и её практическое применение 310
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3785864
求助须知:如何正确求助?哪些是违规求助? 3331212
关于积分的说明 10250565
捐赠科研通 3046660
什么是DOI,文献DOI怎么找? 1672149
邀请新用户注册赠送积分活动 801039
科研通“疑难数据库(出版商)”最低求助积分说明 759979