Fenofibrate Protects Cardiomyocytes from Hypoxia/Reperfusion- and High Glucose-Induced Detrimental Effects.
Fenofibrate Protects Cardiomyocytes from Hypoxia/Reperfusion- and High Glucose-Induced Detrimental Effects.
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DOI：
10.1155/2021/8895376
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发表时间：
2021
期刊：
影响因子：
2.9
通讯作者：
Ibarra-Lara L
中科院分区：
文献类型：
--
作者：
Cortes-Lopez F;Sanchez-Mendoza A;Centurion D;Cervantes-Perez LG;Castrejon-Tellez V;Del Valle-Mondragon L;Soria-Castro E;Ramirez V;Sanchez-Lopez A;Pastelin-Hernandez G;Garcia-Niño WR;Sanchez-Aguilar M;Ibarra-Lara L
心肌细胞中由高糖（HG）、缺氧/再灌注（H/R）以及这两种条件的共存引起的病变与活性氧（ROS）的过度产生有关，从而对心肌细胞中的大分子以及其超微结构造成不可逆的损伤。非诺贝特是一种过氧化物酶体增殖物激活受体α（PPARα）激动剂，可促进对抗心脏损伤的有益活性。因此，本工作的目的是确定非诺贝特在暴露于HG、H/R和HG+H/R的心肌细胞中的潜在保护作用。将心肌细胞培养物分为四个主要组：（1）对照组（CT），（2）HG（25 mM），（3）H/R和（4）HG+H/R。我们的研究结果表明，在心肌细胞经历HG，H/R，和这两种条件下，细胞活力下降，而非诺贝特提高细胞活力在每种情况下。非诺贝特还降低ROS产生以及烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NADPH）亚基表达。在抗氧化防御方面，超氧化物歧化酶（SOD Cu 2 +/Zn 2+和SOD Mn 2+）、过氧化氢酶和抗氧化能力在HG、H/R和HG+H/R暴露的心肌细胞中降低，而非诺贝特增加这些参数。核因子红细胞2相关因子2（Nrf 2）的表达显着增加，在处理的细胞，而病理增加其抑制剂Keap 1的表达。氧化应激诱导的线粒体损伤在非诺贝特暴露的心肌细胞中较低。内皮型一氧化氮合酶也有利于心肌细胞与非诺贝特治疗。我们的研究结果表明，非诺贝特保持抗氧化状态和超微结构在心肌细胞进行HG，H/R，HG+H/R防止损伤的基本大分子参与心肌细胞的正常功能。
Lesions caused by high glucose (HG), hypoxia/reperfusion (H/R), and the coexistence of both conditions in cardiomyocytes are linked to an overproduction of reactive oxygen species (ROS), causing irreversible damage to macromolecules in the cardiomyocyte as well as its ultrastructure. Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist, promotes beneficial activities counteracting cardiac injury. Therefore, the objective of this work was to determine the potential protective effect of fenofibrate in cardiomyocytes exposed to HG, H/R, and HG+H/R. Cardiomyocyte cultures were divided into four main groups: (1) control (CT), (2) HG (25 mM), (3) H/R, and (4) HG+H/R. Our results indicate that cell viability decreases in cardiomyocytes undergoing HG, H/R, and both conditions, while fenofibrate improves cell viability in every case. Fenofibrate also decreases ROS production as well as nicotinamide adenine dinucleotide phosphate oxidase (NADPH) subunit expression. Regarding the antioxidant defense, superoxide dismutase (SOD Cu2+/Zn2+ and SOD Mn2+), catalase, and the antioxidant capacity were decreased in HG, H/R, and HG+H/R-exposed cardiomyocytes, while fenofibrate increased those parameters. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) increased significantly in treated cells, while pathologies increased the expression of its inhibitor Keap1. Oxidative stress-induced mitochondrial damage was lower in fenofibrate-exposed cardiomyocytes. Endothelial nitric oxide synthase was also favored in cardiomyocytes treated with fenofibrate. Our results suggest that fenofibrate preserves the antioxidant status and the ultrastructure in cardiomyocytes undergoing HG, H/R, and HG+H/R preventing damage to essential macromolecules involved in the proper functioning of the cardiomyocyte.
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DOI：
10.1056/nejmoa1001288
发表时间：
2010-07-15
期刊：
The New England journal of medicine
影响因子：
--
作者：
ACCORD Study Group;ACCORD Eye Study Group;Chew EY;Ambrosius WT;Davis MD;Danis RP;Gangaputra S;Greven CM;Hubbard L;Esser BA;Lovato JF;Perdue LH;Goff DC Jr;Cushman WC;Ginsberg HN;Elam MB;Genuth S;Gerstein HC;Schubart U;Fine LJ
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Fine LJ
DOI：
10.3390/molecules22010031
发表时间：
2016-12-28
期刊：
Molecules (Basel, Switzerland)
影响因子：
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作者：
Ibarra-Lara L;Sánchez-Aguilar M;Sánchez-Mendoza A;Del Valle-Mondragón L;Soria-Castro E;Carreón-Torres E;Díaz-Díaz E;Vázquez-Meza H;Guarner-Lans V;Rubio-Ruiz ME
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Rubio-Ruiz ME
影响因子：
3
作者：
Ibarra-Lara, Luz;Hong, Enrique;Sanchez-Mendoza, Alicia
通讯作者：
Sanchez-Mendoza, Alicia
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影响因子：
5.4
作者：
Biddlestone J;Bandarra D;Rocha S
通讯作者：
Rocha S
DOI：
10.1083/jcb.201102095
发表时间：
2011-07-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Finkel T
通讯作者：
Finkel T