Empagliflozin attenuates doxorubicin-induced cardiotoxicity by inhibiting the JNK signaling pathway

恩帕吉菲 心脏毒性 阿霉素 药理学 医学 信号转导 癌症研究 化学 化疗 内科学 内分泌学 糖尿病 生物化学 2型糖尿病
作者
Hsien‐Yuan Chang,Hsiao-Chun Hsu,Yi‐Hsien Fang,Ping‐Yen Liu,Yen-Wen Liu
出处
期刊:Biomedicine & Pharmacotherapy [Elsevier BV]
卷期号:176: 116759-116759 被引量:3
标识
DOI:10.1016/j.biopha.2024.116759
摘要

Sodium-glucose cotransporter-2 inhibitors, such as empagliflozin, are pivotal therapies for heart failure. However, the effect of empagliflozin on doxorubicin-related cardiac dysfunction remains unclear. Human induced pluripotent stem cell- and embryonic stem cell-derived cardiomyocytes were used to investigate the direct effect of empagliflozin on human cardiomyocytes. Then, the c-Jun amino-terminal kinases (JNK) inhibitor SP600125 was administered to the doxorubicin cardiotoxicity model in vitro and in vivo to investigate the role of JNK in empagliflozin. In human stem cell-derived cardiomyocytes, pretreatment with empagliflozin attenuated doxorubicin-induced cleavage of caspase 3 and other apoptosis markers. Empagliflozin significantly attenuated doxorubicin-induced phosphorylation of JNK and p38. Inhibiting the phosphorylation of JNK (SP600125) or STAT3 attenuated doxorubicin-induced apoptosis, but inhibiting the phosphorylation of p38 did not. SP600125 inhibits the phosphorylation of STAT3 (S727), and a STAT3 (Y705) inhibitor also inhibits the phosphorylation of JNK. Empagliflozin and SP600125 attenuated doxorubicin-induced increases in reactive oxygen species (ROS) and decreases in oxidized nicotinamide adenine dinucleotide (NAD+). In animal studies, empagliflozin and SP600125 attenuated doxorubicin-induced cardiac dysfunction and fibrosis. Empagliflozin attenuated doxorubicin-induced apoptosis by inhibiting the phosphorylation of JNK and its downstream signaling pathways, including ROS and NAD+.
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
PDF的下载单位、IP信息已删除 (2025-6-4)

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
einuo完成签到,获得积分10
刚刚
AKYDXS完成签到,获得积分10
3秒前
昏睡的蟠桃应助Llllll采纳,获得200
3秒前
科研通AI2S应助hao采纳,获得10
3秒前
4秒前
4秒前
香蕉觅云应助阿湫采纳,获得10
5秒前
星辰大海应助星辰采纳,获得10
5秒前
阿卡宁完成签到,获得积分10
5秒前
lzw完成签到 ,获得积分10
5秒前
沉静烧仙草完成签到,获得积分20
6秒前
烟花应助嘉嘉琦采纳,获得10
6秒前
隐形曼青应助科研通管家采纳,获得10
6秒前
Hello应助科研通管家采纳,获得10
7秒前
Ava应助科研通管家采纳,获得10
7秒前
上官若男应助科研通管家采纳,获得10
7秒前
7秒前
赘婿应助科研通管家采纳,获得10
7秒前
烟花应助科研通管家采纳,获得10
7秒前
FashionBoy应助科研通管家采纳,获得10
7秒前
英俊的铭应助科研通管家采纳,获得10
7秒前
在水一方应助科研通管家采纳,获得10
7秒前
accepted应助科研通管家采纳,获得10
7秒前
脑洞疼应助科研通管家采纳,获得10
7秒前
7秒前
cdh1994应助kcmat采纳,获得10
7秒前
我是老大应助科研通管家采纳,获得10
7秒前
乐乐应助科研通管家采纳,获得10
7秒前
FashionBoy应助科研通管家采纳,获得10
7秒前
7秒前
上官若男应助科研通管家采纳,获得10
7秒前
7秒前
7秒前
7秒前
我是老大应助科研通管家采纳,获得30
7秒前
脑洞疼应助科研通管家采纳,获得20
8秒前
科目三应助科研通管家采纳,获得30
8秒前
8秒前
完美世界应助科研通管家采纳,获得10
8秒前
8秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
Research on Disturbance Rejection Control Algorithm for Aerial Operation Robots 500
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 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 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038524
求助须知:如何正确求助?哪些是违规求助? 3576221
关于积分的说明 11374737
捐赠科研通 3305912
什么是DOI,文献DOI怎么找? 1819354
邀请新用户注册赠送积分活动 892688
科研通“疑难数据库(出版商)”最低求助积分说明 815048