Sulforaphane regulates AngII-induced podocyte oxidative stress injury through the Nrf2-Keap1/ho-1/ROS pathway.

IF 3 3区 医学 Q1 UROLOGY & NEPHROLOGY Renal Failure Pub Date : 2024-12-01 Epub Date: 2024-10-17 DOI:10.1080/0886022X.2024.2416937
Wen Lu
{"title":"Sulforaphane regulates AngII-induced podocyte oxidative stress injury through the Nrf2-Keap1/ho-1/ROS pathway.","authors":"Wen Lu","doi":"10.1080/0886022X.2024.2416937","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the therapeutic effects of sulforaphane and the role of the Nrf2-Keap1/HO-1/ROS pathway in AngII-induced oxidative stress in podocyte injury.</p><p><strong>Methods: </strong>Mouse mpc5 podocytes were divided into four groups: control (Con), AngII, AngII + sulforaphane (AngII + SFN), and control + sulforaphane (Con + SFN). Western blotting was used to detect protein expression of Nrf2-Keap1, antioxidant enzyme HO-1, and apoptosis-related proteins. ROS levels were measured using a ROS assay kit, and cell survival and viability were assayed using the CCK-8 kit. Molecular interactions between Nrf2 and sulforaphane were analyzed computationally.</p><p><strong>Results: </strong>Compared with the Con group, podocytes treated with AngII alone exhibited inhibited proliferation, reduced cell viability, lower Bcl-2 expression, and higher cleaved caspase 3 expression. In the presence of sulforaphane, AngII group showed a mild inhibition on podocyte proliferation but did not induce the aforementioned changes in Bcl-2 and cleaved caspase 3 expression. Similarly, compared to the Con group, AngII treatment alone had lower Nrf2 expression and higher Keap1 expression in podocytes, accompanied by a significant decrease in ROS content. However, in the presence of sulforaphane, AngII failed to induce increases in Nrf2 and a decrease in Keap1 expression, as well as ROS levels. Furthermore, cells treated with sulforaphane exhibited higher HO-1 levels than control cells, and co-incubation with AngII did not alter HO-1 levels. Computational modeling revealed hydrophobic interactions between sulforaphane and the amino acid LYS-462 of Nrf2, as well as hydrogen bonding with amino acid HIS-465. The binding score between sulforaphane and Nrf2 was -4.7.</p><p><strong>Conclusion: </strong>Sulforaphane alleviated AngII-induced podocyte oxidative stress injury <i>via</i> the Nrf2-Keap1/HO-1/ROS pathway, providing new insights into therapeutic compounds for mitigating chronic kidney disease.</p>","PeriodicalId":20839,"journal":{"name":"Renal Failure","volume":null,"pages":null},"PeriodicalIF":3.0000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488169/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Renal Failure","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/0886022X.2024.2416937","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/17 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Objective: This study aimed to investigate the therapeutic effects of sulforaphane and the role of the Nrf2-Keap1/HO-1/ROS pathway in AngII-induced oxidative stress in podocyte injury.

Methods: Mouse mpc5 podocytes were divided into four groups: control (Con), AngII, AngII + sulforaphane (AngII + SFN), and control + sulforaphane (Con + SFN). Western blotting was used to detect protein expression of Nrf2-Keap1, antioxidant enzyme HO-1, and apoptosis-related proteins. ROS levels were measured using a ROS assay kit, and cell survival and viability were assayed using the CCK-8 kit. Molecular interactions between Nrf2 and sulforaphane were analyzed computationally.

Results: Compared with the Con group, podocytes treated with AngII alone exhibited inhibited proliferation, reduced cell viability, lower Bcl-2 expression, and higher cleaved caspase 3 expression. In the presence of sulforaphane, AngII group showed a mild inhibition on podocyte proliferation but did not induce the aforementioned changes in Bcl-2 and cleaved caspase 3 expression. Similarly, compared to the Con group, AngII treatment alone had lower Nrf2 expression and higher Keap1 expression in podocytes, accompanied by a significant decrease in ROS content. However, in the presence of sulforaphane, AngII failed to induce increases in Nrf2 and a decrease in Keap1 expression, as well as ROS levels. Furthermore, cells treated with sulforaphane exhibited higher HO-1 levels than control cells, and co-incubation with AngII did not alter HO-1 levels. Computational modeling revealed hydrophobic interactions between sulforaphane and the amino acid LYS-462 of Nrf2, as well as hydrogen bonding with amino acid HIS-465. The binding score between sulforaphane and Nrf2 was -4.7.

Conclusion: Sulforaphane alleviated AngII-induced podocyte oxidative stress injury via the Nrf2-Keap1/HO-1/ROS pathway, providing new insights into therapeutic compounds for mitigating chronic kidney disease.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
红豆杉通过Nrf2-Keap1/ho-1/ROS途径调节AngII诱导的荚膜氧化应激损伤
研究目的本研究旨在探讨莱菔硫烷的治疗作用以及 Nrf2-Keap1/HO-1/ROS 通路在 AngII 诱导的荚膜细胞氧化应激损伤中的作用:方法:将小鼠mpc5荚膜细胞分为四组:对照组(Con)、AngⅡ组、AngⅡ+苜蓿素组(AngⅡ+SFN)和对照组+苜蓿素组(Con+SFN)。用 Western 印迹法检测 Nrf2-Keap1、抗氧化酶 HO-1 和细胞凋亡相关蛋白的表达。使用 ROS 检测试剂盒测量 ROS 水平,使用 CCK-8 试剂盒检测细胞存活率和活力。通过计算分析了 Nrf2 与红豆杉素之间的分子相互作用:结果:与 Con 组相比,单用 AngII 处理的荚膜细胞增殖受抑制,细胞存活率降低,Bcl-2 表达降低,裂解 Caspase 3 表达升高。在莱菔硫烷存在的情况下,AngII 组对荚膜细胞增殖有轻微抑制作用,但并未引起上述 Bcl-2 和裂解 Caspase 3 表达的变化。同样,与 Con 组相比,单独 AngII 处理组的荚膜细胞中 Nrf2 表达较低,Keap1 表达较高,同时 ROS 含量显著降低。然而,在有莱菔硫烷存在的情况下,AngII 不能诱导 Nrf2 表达的增加和 Keap1 表达的降低,也不能诱导 ROS 含量的降低。此外,与对照细胞相比,用莱菔硫烷处理过的细胞表现出更高的 HO-1 水平,而与 AngII 共同作用也不会改变 HO-1 的水平。计算模型显示,莱菔硫烷与Nrf2的氨基酸LYS-462之间存在疏水相互作用,并与氨基酸HIS-465之间存在氢键作用。结论:结论:红景天通过Nrf2-Keap1/HO-1/ROS途径缓解了AngⅡ诱导的荚膜氧化应激损伤,为治疗慢性肾病提供了新的思路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Renal Failure
Renal Failure 医学-泌尿学与肾脏学
CiteScore
3.90
自引率
13.30%
发文量
374
审稿时长
1 months
期刊介绍: Renal Failure primarily concentrates on acute renal injury and its consequence, but also addresses advances in the fields of chronic renal failure, hypertension, and renal transplantation. Bringing together both clinical and experimental aspects of renal failure, this publication presents timely, practical information on pathology and pathophysiology of acute renal failure; nephrotoxicity of drugs and other substances; prevention, treatment, and therapy of renal failure; renal failure in association with transplantation, hypertension, and diabetes mellitus.
期刊最新文献
The use of urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin for diagnosis of hepato-renal syndrome in advanced cirrhotic patients. Identification of common and specific fibrosis-related genes in three common chronic kidney diseases. A Mendelian randomization study: physical activities and chronic kidney disease. Association between normal saline infusion volume in the emergency department and acute kidney injury in heat stroke patients: a multicenter retrospective study. Association of frequent intradialytic hypotension with the clinical outcomes of patients on hemodialysis: a prospective cohort study.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1