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!

Supraphysiological levels of testosterone induces endothelial injury via increasing generation of reactive oxygen species and ERK1/2 activation

活性氧 超氧化物歧化酶 超氧化物 内科学 内皮功能障碍 内分泌学 脐静脉 内皮干细胞 生物 氧化应激 氮氧化物4 内皮 NADPH氧化酶 炎症 细胞内 分子生物学 细胞生物学 生物化学 医学 体外
作者
Juliano Alves,Rafael M. Costa,Wanessa M.C. Awata,Shubhnita Singh,Ariane Bruder‐Nascimento,Gabriela Rodrigues Barbosa,Thiago Bruder‐Nascimento
出处
期刊:Physiology [American Physiological Society]
卷期号:38 (S1)
标识
DOI:10.1152/physiol.2023.38.s1.5733006
摘要

Introduction: High levels of testosterone (Testo) is associated with higher cardiovascular risk by positively modulate the generation of reactive oxygen species (ROS) and inflammatory response. Excessive ROS generation by NADPH oxidases (NOX, major source of ROS in the vasculature) leads to endothelial dysfunction, apoptosis, and inflammation. However, the intracellular mechanisms whereby supraphysiological levels of Testo promote cardiovascular damage are still ill defined. We sought to determine whether supraphysiological levels of Testo induces endothelial cell dysfunction via ROS generation and ERK1/2 activation. Methods: To study whether Testo present the same effects independent on endothelial cell type, we used Primary Human Mesenteric vascular Endothelial Cells (HMEC) and Human Umbilical Vein Endothelial Cells (HUVEC). Cells were stimulated with Testo (10 −7 M, for different time points) in the presence or absence of superoxide dismutase mimetic (Tempol, 10 -4 M, for 30 min). NOX activity, gene expression, and protein expression were determined pharmacological assays and immunoblotting, respectively. Results: Testo increased superoxide anion (O 2 − ) generation in HMEC and HUVEC at short (10 min) stimulation times, which was abolished by superoxide dismutase (SOD) mimetic [(% of control) Ctrl: 100.0 ± 0.0 n=5 vs Testo: 363.2 ± 19.77 n=6 vs. Tempol+Testo: 156.7 ± 12.12 n=6, *P<0.05]. Furthermore, long-term treatment (24 h) of endothelial cells with Testo increased Nox4 expression at gene (2.44-Fold change) and protein levels [(% of control) Ctrl: 100.0 ± 0.0 n=4 vs. Testo: 157.3 ± 4.49 n=4, *P<0.05]. Testo did not affect Nox1, Nox2, and Nox5 expressions. Furthermore, Testo increased ERK1/2 phosphorylation at 10 minutes and promoted endothelial cell inflammation at 8h, characterized by increased ICAM-1(6.49-Fold changes) and VCAM-1 [(1.42-Fold changes) gene expressions. To confirm that Testo-induced ROS production is leading to endothelial injury via ERK1/2, we treated endothelial cells with Tempol prior Testo treatment. Interestingly, superoxide dismutase mimetic prevented ERK1/2 phosphorylation induced by Testo [(% of control) Testo: 161.2 ± 11.39 n=5 vs. Tempol+Testo: 91.45 ± 9.61 n=5, *P<0.05]. Conclusion: These data indicate that supraphysiological levels of testosterone induce endothelial dysfunction via ROS generation and inflammatory response. Our data helps understanding the intracellular mechanisms that justify the cardiovascular damage caused by supraphysiological doses of testosterone and places antioxidant therapy as a possible pharmacological approach to treat patients with dysregulated testosterone levels. 2022/00103-3, São Paulo Research Foundation (FAPESP). NHLBI-R00 (R00HL14013903), AHA-CDA (CDA857268), Vascular Medicine Institute, the Hemophilia Center of Western Pennsylvania Vitalant, and Children's Hospital of Pittsburgh of the UPMC Health System. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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
pokemeow完成签到,获得积分10
9秒前
搜集达人应助科研通管家采纳,获得10
17秒前
Jasper应助科研通管家采纳,获得10
17秒前
pokemeow发布了新的文献求助10
30秒前
YY完成签到,获得积分0
45秒前
别找了睡觉吧完成签到 ,获得积分10
50秒前
汉堡包应助hhhhhhhm采纳,获得10
57秒前
薄荷小新完成签到 ,获得积分10
1分钟前
情怀应助甜心心采纳,获得10
1分钟前
闪闪的从彤完成签到 ,获得积分10
1分钟前
雨天爱吃冰淇淋完成签到 ,获得积分10
1分钟前
在水一方应助壮壮采纳,获得10
1分钟前
大个应助无糖零脂采纳,获得10
1分钟前
1分钟前
壮壮发布了新的文献求助10
1分钟前
未青易完成签到 ,获得积分10
1分钟前
2分钟前
明理丹烟应助科研通管家采纳,获得10
2分钟前
科研通AI2S应助科研通管家采纳,获得10
2分钟前
NexusExplorer应助科研通管家采纳,获得10
2分钟前
科研通AI2S应助科研通管家采纳,获得10
2分钟前
明理丹烟应助科研通管家采纳,获得10
2分钟前
英姑应助科研通管家采纳,获得10
2分钟前
汉堡包应助科研通管家采纳,获得10
2分钟前
科研通AI2S应助qqq采纳,获得10
2分钟前
小马日常挨打完成签到 ,获得积分10
3分钟前
苏航完成签到,获得积分20
3分钟前
qqq完成签到,获得积分10
3分钟前
3分钟前
qqq发布了新的文献求助10
3分钟前
钰姝完成签到,获得积分20
3分钟前
苏航发布了新的文献求助10
3分钟前
思源应助Cassel采纳,获得10
3分钟前
小蘑菇应助Chloe采纳,获得10
4分钟前
端庄的访枫完成签到 ,获得积分10
4分钟前
SciGPT应助ylky采纳,获得50
4分钟前
可爱的函函应助Jing采纳,获得10
4分钟前
4分钟前
科研通AI2S应助科研通管家采纳,获得10
4分钟前
天天快乐应助MoonFlows采纳,获得10
4分钟前
高分求助中
中国国际图书贸易总公司40周年纪念文集 大事记1949-1987 2000
TM 5-855-1(Fundamentals of protective design for conventional weapons) 1000
草地生态学 880
Threaded Harmony: A Sustainable Approach to Fashion 799
Basic Modern Theory of Linear Complex Analytic 𝑞-Difference Equations 510
中国有机(类)肥料 500
Queer Politics in Times of New Authoritarianisms: Popular Culture in South Asia 500
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 3059518
求助须知:如何正确求助?哪些是违规求助? 2715495
关于积分的说明 7445189
捐赠科研通 2361002
什么是DOI,文献DOI怎么找? 1251087
科研通“疑难数据库(出版商)”最低求助积分说明 607698
版权声明 596448