[Microtubule-associated tumor suppressor 1 inhibits hemin-induced apoptosis of vascular endothelial cells via hemeoxygenase 1].

Q3 Medicine
生理学报 Pub Date : 2024-04-25
Sheng-Yun Wu, Ke-Ru Cheng, Yan-Yun Zhou, Yin-Fang Wang
{"title":"[Microtubule-associated tumor suppressor 1 inhibits hemin-induced apoptosis of vascular endothelial cells via hemeoxygenase 1].","authors":"Sheng-Yun Wu, Ke-Ru Cheng, Yan-Yun Zhou, Yin-Fang Wang","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>This study aimed to investigate the effects of microtubule associated tumor suppressor 1 (MTUS1) on hemeoxygenase 1 (HMOX1) expression and hemin-induced apoptosis of vascular endothelial cells and its regulatory mechanism. RNA sequencing, RT-qPCR and Western blot were used to assess altered genes of hemin binding proteins, the expression of cAMP response element-binding protein (CREB) and nuclear respiratory factor 2 (NRF2), hemin-induced HMOX1 expression in MTUS1 knockdown human umbilical vein endothelial cells (HUVEC), and the effect of overexpression of CREB and NRF2 on HMOX1 expression in MTUS1 knockdown 293T cells. The effect of MTUS1 or HMOX1 knockdown on hemin-induced apoptosis in HUVEC, and the overexpression of NRF2 on hemin-induced apoptosis in MTUS1 knockdown 293T cells were assayed with CCK8 and Western blot. The results showed that MTUS1 was knocked down significantly in HUVEC by siRNA (P < 0.01), accompanied by decreased HMOX1 expression (P < 0.01). The increased HMOX1 expression induced by hemin was also inhibited by MTUS1 knockdown (P < 0.01). And the apoptosis of HUVEC induced by hemin was amplified by MTUS1 or HMOX1 knockdown (P < 0.01). Moreover the expression of CREB and NRF2 were both inhibited by MTUS1 knockdown in HUVEC (P < 0.01). The decreased HMOX1 regulated by MTUS1 knockdown could be rescued partly by overexpression of NRF2 (P < 0.01), however, not by overexpression of CREB. And the MTUS1 knockdown mediated decreased 293T cells viability induced by hemin could be partly rescued by NRF2 overexpression (P < 0.01). These results suggest that MTUS1 can inhibit hemin-induced apoptosis of HUVEC, and the mechanism maybe related to MTUS1/NRF2/HMOX1 pathway.</p>","PeriodicalId":7134,"journal":{"name":"生理学报","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"生理学报","FirstCategoryId":"1087","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0

Abstract

This study aimed to investigate the effects of microtubule associated tumor suppressor 1 (MTUS1) on hemeoxygenase 1 (HMOX1) expression and hemin-induced apoptosis of vascular endothelial cells and its regulatory mechanism. RNA sequencing, RT-qPCR and Western blot were used to assess altered genes of hemin binding proteins, the expression of cAMP response element-binding protein (CREB) and nuclear respiratory factor 2 (NRF2), hemin-induced HMOX1 expression in MTUS1 knockdown human umbilical vein endothelial cells (HUVEC), and the effect of overexpression of CREB and NRF2 on HMOX1 expression in MTUS1 knockdown 293T cells. The effect of MTUS1 or HMOX1 knockdown on hemin-induced apoptosis in HUVEC, and the overexpression of NRF2 on hemin-induced apoptosis in MTUS1 knockdown 293T cells were assayed with CCK8 and Western blot. The results showed that MTUS1 was knocked down significantly in HUVEC by siRNA (P < 0.01), accompanied by decreased HMOX1 expression (P < 0.01). The increased HMOX1 expression induced by hemin was also inhibited by MTUS1 knockdown (P < 0.01). And the apoptosis of HUVEC induced by hemin was amplified by MTUS1 or HMOX1 knockdown (P < 0.01). Moreover the expression of CREB and NRF2 were both inhibited by MTUS1 knockdown in HUVEC (P < 0.01). The decreased HMOX1 regulated by MTUS1 knockdown could be rescued partly by overexpression of NRF2 (P < 0.01), however, not by overexpression of CREB. And the MTUS1 knockdown mediated decreased 293T cells viability induced by hemin could be partly rescued by NRF2 overexpression (P < 0.01). These results suggest that MTUS1 can inhibit hemin-induced apoptosis of HUVEC, and the mechanism maybe related to MTUS1/NRF2/HMOX1 pathway.

[微管相关肿瘤抑制因子 1 通过血红素氧合酶 1 抑制血红素诱导的血管内皮细胞凋亡】。]
本研究旨在探讨微管相关肿瘤抑制因子1(MTUS1)对血红素氧合酶1(HMOX1)表达和血红素诱导血管内皮细胞凋亡的影响及其调控机制。采用RNA测序、RT-qPCR和Western blot等方法评估了MTUS1敲除的人脐静脉内皮细胞(HUVEC)中血红素结合蛋白基因的改变、cAMP反应元件结合蛋白(CREB)和核呼吸因子2(NRF2)的表达、血红素诱导的HMOX1的表达,以及过表达CREB和NRF2对MTUS1敲除的293T细胞中HMOX1表达的影响。CCK8和Western blot检测了MTUS1或HMOX1敲除对海明诱导的HUVEC细胞凋亡的影响,以及NRF2过表达对海明诱导的MTUS1敲除293T细胞凋亡的影响。结果表明,siRNA能显著敲除HUVEC中的MTUS1(P<0.01),同时HMOX1的表达也降低(P<0.01)。MTUS1敲除也抑制了hemin诱导的HMOX1表达增加(P < 0.01)。MTUS1或HMOX1敲除后,hemin诱导的HUVEC细胞凋亡被放大(P < 0.01)。此外,MTUS1敲除还抑制了CREB和NRF2在HUVEC中的表达(P < 0.01)。过量表达 NRF2 可以部分缓解 MTUS1 敲除导致的 HMOX1 减少(P < 0.01),但过量表达 CREB 则无法缓解。而NRF2的过量表达可部分缓解MTUS1敲除介导的海明诱导的293T细胞活力下降(P < 0.01)。这些结果表明,MTUS1能抑制hemin诱导的HUVEC细胞凋亡,其机制可能与MTUS1/NRF2/HMOX1通路有关。
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 求助全文
来源期刊
生理学报
生理学报 Medicine-Medicine (all)
CiteScore
1.20
自引率
0.00%
发文量
4820
期刊介绍: Acta Physiologica Sinica (APS) is sponsored by the Chinese Association for Physiological Sciences and Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences (CAS), and is published bimonthly by the Science Press, China. APS publishes original research articles in the field of physiology as well as research contributions from other biomedical disciplines and proceedings of conferences and symposia of physiological sciences. Besides “Original Research Articles”, the journal also provides columns as “Brief Review”, “Rapid Communication”, “Experimental Technique”, and “Letter to the Editor”. Articles are published in either Chinese or English according to authors’ submission.
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信