Canagliflozin Attenuates Lipotoxicity in Cardiomyocytes by Inhibiting Inflammation and Ferroptosis through Activating AMPK Pathway

被引:50
|
作者
Zhang, Wanqiu [1 ,2 ]
Lu, Jinghua [1 ,2 ]
Wang, Yangyang [1 ,2 ,3 ]
Sun, Pengbo [1 ,2 ,3 ]
Gao, Tong [1 ,2 ]
Xu, Naihan [1 ,2 ,3 ]
Zhang, Yaou [1 ,2 ,3 ]
Xie, Weidong [1 ,2 ,3 ]
机构
[1] Tsinghua Univ, Shenzhen Int Grad Sch, State Key Lab Chem Oncogen, Shenzhen 518055, Peoples R China
[2] Tsinghua Univ, Inst Biopharmaceut & Hlth Engn, Shenzhen Int Grad Sch, Key Lab Hlth Sci & Technol, Shenzhen 518055, Peoples R China
[3] Tsinghua Univ, Open FIESTA Ctr, Shenzhen Int Grad Sch, Shenzhen 518055, Peoples R China
关键词
canagliflozin; lipotoxicity; cardiomyocytes; inflammation; ferroptosis; AMPK; CARDIOMYOPATHY;
D O I
10.3390/ijms24010858
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Diabetic cardiomyopathy (DCM) is a myocardial disease independent of other cardiovascular diseases, such as coronary heart disease, hypertension, etc. Lipotoxicity is closely related to DCM. In this study, we investigated the mechanism of lipid metabolism disturbance in DCM in HL-1 cells. Through bioinformatics and Western blotting analysis, we found that canagliflozin (CAN) significantly inhibited the expression of inflammatory factors cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Ferroptosis is mediated by lipid peroxidation. We demonstrated the presence of ferroptosis in cardiomyocytes by detecting intracellular Fe2+ content and the levels of reactive oxygen species (ROS), malondialdehyde (MDA), reduced glutathione (GSH), and mitochondrial membrane potential (MMP). CAN could significantly regulate the indicators of ferroptosis. By using specific inhibitors celecoxib (coxib), S-methylisothiourea sulfate (SMT), Ferrostatin-1 (Fer-1), and Compound C, we further found that CAN regulated inflammation and ferroptosis through AMP-activated protein (AMPK), and inflammation interacted with ferroptosis. Our study indicated that CAN attenuated lipotoxicity in cardiomyocytes by regulating inflammation and ferroptosis through activating the AMPK pathway. This study provides a new direction of myocardial lipotoxicity and some new information for the treatment of DCM.
引用
收藏
页数:14
相关论文
共 50 条
  • [1] Canagliflozin attenuates lipotoxicity in cardiomyocytes and protects diabetic mouse hearts by inhibiting the mTOR/HIF-1α pathway
    Sun, Pengbo
    Wang, Yangyang
    Ding, Yipei
    Luo, Jingyi
    Zhong, Jin
    Xu, Naihan
    Zhang, Yaou
    Xie, Weidong
    ISCIENCE, 2021, 24 (06)
  • [2] Sulforaphane attenuates obesity by inhibiting adipogenesis and activating the AMPK pathway in obese mice
    Choi, Kyeong-Mi
    Lee, Youn-Sun
    Kim, Wonkyun
    Kim, Seung Jung
    Shin, Kyong-Oh
    Yu, Ji-Yeon
    Lee, Mi Kyeong
    Lee, Yong-Moon
    Hong, Jin Tae
    Yun, Yeo-Pyo
    Yoo, Hwan-Soo
    JOURNAL OF NUTRITIONAL BIOCHEMISTRY, 2014, 25 (02): : 201 - 207
  • [3] Lipotoxicity Induces Cardiomyocyte Ferroptosis via Activating the STING Pathway
    Chen, Qian
    Wang, Yina
    Wang, Jiafu
    Ouyang, Xiaolan
    Zhong, Junlin
    Huang, Yao
    Huang, Zhuoshan
    Zheng, Benrong
    Peng, Long
    Tang, Xixiang
    Li, Suhua
    ANTIOXIDANTS & REDOX SIGNALING, 2025, 42 (4-6) : 184 - 198
  • [4] Ursolic acid protects hepatocytes against lipotoxicity through activating autophagy via an AMPK pathway
    Meng, Fanyu
    Ning, Hua
    Sun, Zongxiang
    Huang, Fangfang
    Li, Yanchuan
    Chu, Xia
    Lu, Huimin
    Sun, Changhao
    Li, Songtao
    JOURNAL OF FUNCTIONAL FOODS, 2015, 17 : 172 - 182
  • [5] Luteolin attenuates Staphylococcus aureus-induced endometritis through inhibiting ferroptosis and inflammation via activating the Nrf2/GPX4 signaling pathway
    Gao, Shouyang
    Gao, Yongjian
    Cai, Lifu
    Qin, Rui
    MICROBIOLOGY SPECTRUM, 2024, 12 (02):
  • [6] Metformin reduces inflammation in diabetic human vitreous by activating AMPK and inhibiting NFκB signaling pathway
    Li, Yue
    Zhou, Tongrong
    Hsu, Andrew
    Edwards, Paul A.
    Gao, Hua
    Qiao, Xiaoxi
    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2019, 60 (09)
  • [7] Irisin Attenuates Osteoarthritis by Inhibiting Apoptosis of Osteocytes Through Activating Erk Signaling Pathway
    Zihao He
    Hanjun Li
    Feng Zhou
    Jingke Du
    Shuhong Zhang
    Tingting Tang
    Zhifeng Yu
    医用生物力学, 2019, 34(S1) (S1) : 51 - 52
  • [8] Irisin Attenuates Osteoarthritis by Inhibiting Apoptosis of Osteocyte through Activating Erk Signaling Pathway
    He, Zihao
    Yu, Zhifeng
    JOURNAL OF BONE AND MINERAL RESEARCH, 2019, 34 : 80 - 81
  • [9] IRISIN ATTENUATES OSTEOARTHRITIS BY INHIBITING APOPTOSIS OF OSTEOCYTES THROUGH ACTIVATING ERK SIGNALING PATHWAY
    He, Z.
    Li, H.
    Zhou, F.
    Han, X.
    Chu, L.
    Zhang, S.
    Tang, T.
    Yu, Z.
    OSTEOARTHRITIS AND CARTILAGE, 2019, 27 : S194 - S194
  • [10] Honokiol attenuates lipotoxicity in hepatocytes via activating SIRT3-AMPK mediated lipophagy
    Liu, Jingxin
    Zhang, Tian
    Zhu, Jianzhong
    Ruan, Shuangchen
    Li, Rongsong
    Guo, Bing
    Lin, Ligen
    CHINESE MEDICINE, 2021, 16 (01)