Polygala fallax Hemsl. ameliorated high glucose-induced podocyte injury by modulating mitochondrial mPTP opening through the SIRT1/PGC-1α pathway.

IF 2.5 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM Archives of Physiology and Biochemistry Pub Date : 2024-09-02 DOI:10.1080/13813455.2024.2392298
Chao Shih-Wei, Bo Chen, Yanqing Mao, Qin Xu, Yige Chen
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Abstract

This study aimed to investigate the effects and molecular mechanism of PF on high glucose (HG)-induced podocyte injury. Results found that PF increased proliferation activity, decreased apoptosis, LDH, and caspase-3 levels, and increased nephrin and podocin expression in HG-induced cells. Similarly, PF improved HG-induced mitochondrial damage, decreased Ca2+ and ROS content, alleviated oxidative stress, inhibited mPTP opening, increased mitochondrial membrane potential, and decreased the expressions of Drp1, Bak, Bax, and Cytc in cytoplasm, increased the expressions of SIRT1, PGC-1α, HSP70, HK2, and Cytc in mitochondria of podocytes. The use of mPTP agonist/blocker and SIRT1 inhibitor confirmed that PF alleviates HG-induced podocyte injury by regulating mitochondrial mPTP opening through SIRT1/PGC-1α. In addition, PF affected HK2-VDAC1 protein binding to regulate mPTP opening via the SIRT1/PGC-1α pathway. In conclusion, PF-regulated HK2-VDAC1 protein binding affected mitochondrial mPTP opening and improved HG-induced podocyte injury through the SIRT1/PGC-1α pathway.

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远志通过 SIRT1/PGC-1α 途径调节线粒体 mPTP 开放,从而改善高血糖诱导的荚膜细胞损伤。
本研究旨在探讨 PF 对高血糖(HG)诱导的荚膜细胞损伤的影响及其分子机制。结果发现,PF 能增加 HG 诱导的荚膜细胞的增殖活性,降低细胞凋亡、LDH 和 caspase-3 水平,增加肾素和荚膜蛋白的表达。同样,PF 可改善 HG 诱导的线粒体损伤,降低 Ca2+ 和 ROS 含量,减轻氧化应激,抑制 mPTP 开放,提高线粒体膜电位,降低细胞质中 Drp1、Bak、Bax 和 Cytc 的表达,提高荚膜细胞线粒体中 SIRT1、PGC-1α、HSP70、HK2 和 Cytc 的表达。使用 mPTP 激动剂/阻断剂和 SIRT1 抑制剂证实,PF 可通过 SIRT1/PGC-1α 调节线粒体 mPTP 开放,从而减轻 HG 诱导的荚膜细胞损伤。此外,PF还影响了HK2-VDAC1蛋白的结合,从而通过SIRT1/PGC-1α途径调节mPTP开放。总之,PF调节HK2-VDAC1蛋白结合影响线粒体mPTP开放,并通过SIRT1/PGC-1α途径改善HG诱导的荚膜细胞损伤。
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来源期刊
Archives of Physiology and Biochemistry
Archives of Physiology and Biochemistry ENDOCRINOLOGY & METABOLISM-PHYSIOLOGY
CiteScore
6.90
自引率
3.30%
发文量
21
期刊介绍: Archives of Physiology and Biochemistry: The Journal of Metabolic Diseases is an international peer-reviewed journal which has been relaunched to meet the increasing demand for integrated publication on molecular, biochemical and cellular aspects of metabolic diseases, as well as clinical and therapeutic strategies for their treatment. It publishes full-length original articles, rapid papers, reviews and mini-reviews on selected topics. It is the overall goal of the journal to disseminate novel approaches to an improved understanding of major metabolic disorders. The scope encompasses all topics related to the molecular and cellular pathophysiology of metabolic diseases like obesity, type 2 diabetes and the metabolic syndrome, and their associated complications. Clinical studies are considered as an integral part of the Journal and should be related to one of the following topics: -Dysregulation of hormone receptors and signal transduction -Contribution of gene variants and gene regulatory processes -Impairment of intermediary metabolism at the cellular level -Secretion and metabolism of peptides and other factors that mediate cellular crosstalk -Therapeutic strategies for managing metabolic diseases Special issues dedicated to topics in the field will be published regularly.
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