亲爱的研友该休息了!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!身体可是革命的本钱,早点休息,好梦!

Sonic hedgehog restrains the ubiquitin-dependent degradation of SP1 to inhibit neuronal/glial senescence associated phenotypes in chemotherapy-induced peripheral neuropathy via the TRIM25-CXCL13 axis

衰老 活性氧 细胞生物学 癌症研究 生物 化学
作者
Ying Zou,Shu Wu,Qian Hu,Haoxian Zhou,Yuanlong Ge,Zhenyu Ju,Sheng‐Kang Luo
出处
期刊:Journal of Advanced Research [Elsevier]
被引量:2
标识
DOI:10.1016/j.jare.2024.03.006
摘要

Chemotherapy-induced peripheral neuropathy (CIPN) is a common complication that affects an increasing number of cancer survivors. However, the current treatment options for CIPN are limited. Paclitaxel (PTX) is a widely used chemotherapeutic drug that induces senescence in cancer cells. While previous studies have demonstrated that Sonic hedgehog (Shh) can counteract cellular dysfunction during aging, its role in CIPN remains unknown. Herein, the aim of this study was to investigate whether Shh activation could inhibits neuronal/glial senescence and alleviates CIPN. We treated ND7/23 neuronal cells and RSC96 Schwann cells with two selective Shh activators (purmorphamine [PUR] and smoothened agonist [SAG]) in the presence of PTX. Additionally, we utilized a CIPN mouse model induced by PTX injection. To assess cellular senescence, we performed a senescence-associated β-galactosidase (SA-β-gal) assay, measured reactive oxygen species (ROS) levels, and examined the expression of P16, P21, and γH2AX. To understand the underlying mechanisms, we conducted ubiquitin assays, LC-MS/MS, H&E staining, and assessed protein expression through Western blotting and immunofluorescence staining. In vitro, we observed that Shh activation significantly alleviated the senescence-related decline in multiple functions included SA-β-gal activity, expression of P16 and P21, cell viability, and ROS accumulation in DRG sensory neurons and Schwann cells after PTX exposure. Furthermore, our in vivo experiments demonstrated that Shh activation significantly reduced axonal degeneration, demyelination, and improved nerve conduction. Mechanistically, we discovered that PTX reduced the protein level of SP1, which was ubiquitinated by the E3 ligase TRIM25 at the lysine 694 (K694), leading to increased CXCL13 expression, and we found that Shh activation inhibited PTX-induced neuronal/glial senescence and CIPN through the TRIM25-SP1-CXCL13 axis. These findings provide evidence for the role of PTX-induced senescence in DRG sensory neurons and Schwann cells, suggesting that Shh could be a potential therapeutic target for CIPN.
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
更新
大幅提高文件上传限制,最高150M (2024-4-1)

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
3秒前
juziyaya应助白佐帅采纳,获得10
13秒前
完美世界应助科研通管家采纳,获得10
15秒前
19秒前
ddfighting发布了新的文献求助10
22秒前
科研小刘发布了新的文献求助10
24秒前
璟焱完成签到 ,获得积分10
26秒前
42秒前
45秒前
YYYY完成签到 ,获得积分10
48秒前
叮咚雨发布了新的文献求助10
49秒前
sora98完成签到 ,获得积分10
55秒前
豆包完成签到 ,获得积分10
1分钟前
Kry4taloL发布了新的文献求助10
1分钟前
HOW完成签到 ,获得积分10
1分钟前
Hello完成签到,获得积分10
1分钟前
JamesPei应助科研通管家采纳,获得20
2分钟前
caca完成签到,获得积分10
2分钟前
斯文败类应助弯碧琼采纳,获得10
2分钟前
orixero应助bixiao采纳,获得30
3分钟前
3分钟前
山止川行完成签到 ,获得积分10
3分钟前
yier发布了新的文献求助10
3分钟前
yier完成签到,获得积分20
3分钟前
灵感大王喵完成签到 ,获得积分10
3分钟前
3分钟前
h0jian09完成签到,获得积分10
4分钟前
4分钟前
脑洞疼应助科研通管家采纳,获得10
4分钟前
Kry4taloL发布了新的文献求助100
4分钟前
hayk发布了新的文献求助10
4分钟前
fendy完成签到,获得积分0
4分钟前
4分钟前
薛定谔的猫完成签到,获得积分10
4分钟前
hayk完成签到,获得积分20
4分钟前
4分钟前
么么么发布了新的文献求助10
5分钟前
么么么完成签到 ,获得积分10
5分钟前
科研小刘发布了新的文献求助10
5分钟前
Tethys完成签到 ,获得积分10
6分钟前
高分求助中
The Young builders of New china : the visit of the delegation of the WFDY to the Chinese People's Republic 1000
юрские динозавры восточного забайкалья 800
English Wealden Fossils 700
Chen Hansheng: China’s Last Romantic Revolutionary 500
宽禁带半导体紫外光电探测器 388
Case Research: The Case Writing Process 300
Global Geological Record of Lake Basins 300
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3142675
求助须知:如何正确求助?哪些是违规求助? 2793563
关于积分的说明 7806917
捐赠科研通 2449815
什么是DOI,文献DOI怎么找? 1303501
科研通“疑难数据库(出版商)”最低求助积分说明 626959
版权声明 601314