ReferenceID 4984

Crocin Improves Endothelial Mitochondrial Dysfunction via GPx1/ROS/KCa3.1 Signal Axis in Diabetes

Front Cell Dev Biol

Mitochondrial dysfunction contributes to excessive reactive oxygen species (ROS) generation, which is a dramatic cause to promote endothelial dysfunction in diabetes. It was previously demonstrated that crocin protected

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Reference Id
4984
Evidence Id
21574
Core Evidence Id
21574
Source Reference Id
3218
Herb2 Reference Id
HBREF004015
Subject Paper Key
HBIN021714_33777959
Pubmed Id
33777959
Doi
10.3389/fcell.2021.651434
Paper Title
Crocin Improves Endothelial Mitochondrial Dysfunction via GPx1/ROS/KCa3.1 Signal Axis in Diabetes
Paper Abstract
Mitochondrial dysfunction contributes to excessive reactive oxygen species (ROS) generation, which is a dramatic cause to promote endothelial dysfunction in diabetes. It was previously demonstrated that crocin protected the endothelium based on its diverse medicinal properties, but its effect on the mitochondrion and the potential mechanism are not fully understood. In this study, mitochondrial function was analyzed during the process of excessive ROS generation in high glucose (HG)-cultured human umbilical vein endothelial cells (HUVECs). The role played by KCa3.1 was further investigated by the inhibition and/or gene silence of KCa3.1 in this process. In addition, nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase 2 (NOX2), superoxide dismutase 1 (SOD1), and glutathione peroxidase 1 (GPx1) were also detected in this study. Our data showed that crocin improved mitochondrial dysfunction and maintained normal mitochondrial morphology by enhancing the mitochondrial membrane potential (MMP), mitochondrial mass, and mitochondrial fusion. Furthermore, KCa3.1 was confirmed to be located in the mitochondrion, and the blockade and/or silencing of KCa3.1 improved mitochondrial dysfunction and reduced excessive ROS generation but did not affect NOX2 and/or the SOD1 system. Intriguingly, it was confirmed that KCa3.1 expression was elevated by ROS overproduction in the endothelium under HG and/or diabetes conditions, while crocin significantly suppressed this elevation by promoting GPx1 and subsequently eliminating ROS generation. In addition, crocin enhanced CD31, thrombomodulin (TM), and p-/t-endothelial nitric oxide synthase (eNOS) expressions as well as NO generation and decreased vascular tone. Hence, crocin improved mitochondrial dysfunction through inhibiting ROS-induced KCa3.1 overexpression in the endothelium, which in turn reduced more ROS generation and final endothelial dysfunction in diabetes.
Journal
Front Cell Dev Biol
Publish Year
2021
Experiment Subject
human; high glucose (hg)-cultured human umbilical vein endothelial cells; huvecs
Experiment Type
Cell Experiment
Phenotype Related
Mitochondrial Dysfunction; Diabetes; Endothelial Dysfunction
Paper Title Cn
Paper Title En
Crocin Improves Endothelial Mitochondrial Dysfunction via GPx1/ROS/KCa3.1 Signal Axis in Diabetes
Bilingual Status
semi_complete