Effects of NRF-1 and PGC-1α cooperation on HIF-1α and rat cardiomyocyte apoptosis under hypoxia

Niu, Nan; Li, Hui; Du, Xiancai; Wang, Chan; Li, Junliang; Yang, Jihui; Liu, Cheng; Yang, Songhao; Zhu, Yazhou; Zhao, Wei

doi:10.1016/j.gene.2022.146565

Cited by 8 publications

(4 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…8-hydroxydeoxyguanine nucleoside is a molecular marker of mtDNA damage. Oxidative stress accelerates cell membrane lipid peroxidation, during which MDA content increases together with an after-consumption reduction in SOD and GSH-PX antioxidant enzymatic activities [ 25 ]. Secondly, PGC-1α regulates the mtDNA biosynthesis.…”

Section: Discussionmentioning

confidence: 99%

Fenofibrate alleviates NAFLD by enhancing the PPARα/PGC-1α signaling pathway coupling mitochondrial function

Wang,

Ying

et al. 2024

BMC Pharmacol Toxicol

View full text Add to dashboard Cite

Background To comprehend the influences of fenofibrate on hepatic lipid accumulation and mitochondrial function-related signaling pathways in mice with non-alcoholic fatty liver disease (NAFLD) secondary to high-fat diets together with free fatty acids-influenced HepG2 cells model. Materials and methods A random allocation of male 6-week C57BL/6J mice into three groups was done, including controls, model (14 weeks of a high-fat diet), and fenofibrate [similar to the model one with administered 0.04 g/(kg.d) fenofibrate by gavage at 11 weeks for 4 weeks] groups, which contained 10 mice each. This study verified NAFLD pathogenesis via mitochondrial functions in hepatic pathological abnormalities, liver index and weight, body weight, serum biochemical indexes, oxidative stress indicators, mitochondrial function indexes, and related signaling pathways. The effect of fenofibrate intervention was investigated in NAFLD model mice. In vitro, four groups based on HepG2 cells were generated, including controls, the FFA model (1.5 mmol/L FFA incubation for 24 h), LV-PGC-1α intervention (similar to the FFA model one after PPARGC1A lentivirus transfection), and LV control intervention (similar to the FFA model one after negative control lentivirus transfection) groups. The study investigated the mechanism of PGC-1α related to lipid decomposition and mitochondrial biosynthesis by Oil red O staining, colorimetry and western blot. Results In vivo experiments, a high-fat diet achieved remarkable changes regarding liver weight, liver index, serum biochemical indicators, oxidative stress indicators, liver pathological changes, mitochondrial function indicators, and body weight of the NAFLD model mice while fenofibrate improved the objective indicators. In the HepG2 cells model, the lipid accumulation increased significantly within the FFA model group, together with aggravated hepatocytic damage and boosted oxidative stress levels. Moreover, FFA induced excessive mitosis into fragmented in mitochondrial morphology, ATP content in cells decreased, mtDNA replication fold decreased, the expression of lipid decomposition protein PPARα reduced, mitochondrial biosynthesis related protein PGC-1α, NRF-1 and TFAM decreased. PGC-1α overexpression inhibited lipid deposition by improving mitochondrial biosynthesis and lipid decomposition. Conclusion Fenofibrate up-regulated PPARα/PGC-1α signaling pathway, promoted mitochondrial β-oxidation, reduced oxidative stress damage and lipid accumulation of liver. PGC-1α overexpression enhanced mitochondrial biosynthesis and ATP production, and reduced HepG2 intracellular accumulation of lipids and oxidative stress.

show abstract

Section: Discussionmentioning

confidence: 99%

Fenofibrate alleviates NAFLD by enhancing the PPARα/PGC-1α signaling pathway coupling mitochondrial function

Wang,

Ying

et al. 2024

BMC Pharmacol Toxicol

View full text Add to dashboard Cite

show abstract

“…Mechanistically, a group of transcription factors including signal transducer and activator of transcription 1(STAT1), signal transducer and activator of transcription 3 (STAT3), NF-κB, interferon regulatory factor 9 (IRF9), nuclear respiratory factor 1 (NRF1), and BCL2 associated transcription factor 1 (BCLAF1) can bind to the HIF1A gene promoter and regulate HIF1A expression ( Gerber and Pober, 2008 ; Wang et al, 2016 ; Park et al, 2017 ; Shao et al, 2020 ; Li Z. L. et al, 2021b ; He et al, 2022 ; Niu et al, 2022 ). Further analysis of the expression of these six transcription factors during ATG7 silencing revealed that STAT1 was the most abundantly expressed in human umbilical vein endothelial cells (HUVECs), followed by IRF9, while the expression of other transcription factors did not change significantly ( Yao et al, 2022 ).…”

Section: Atg7 Regulates Angiogenesis Via Non-autophagic Pathwaysmentioning

confidence: 99%

Role of ATG7-dependent non-autophagic pathway in angiogenesis

Chen,

Liang,

et al. 2024

Front. Pharmacol.

View full text Add to dashboard Cite

ATG7, one of the core proteins of autophagy, plays an important role in various biological processes, including the regulation of autophagy. While clear that autophagy drives angiogenesis, the role of ATG7 in angiogenesis remains less defined. Several studies have linked ATG7 with angiogenesis, which has long been underappreciated. The knockdown of ATG7 gene in cerebrovascular development leads to angiogenesis defects. In addition, specific knockout of ATG7 in endothelial cells results in abnormal development of neovascularization. Notably, the autophagy pathway is not necessary for ATG7 regulation of angiogenesis, while the ATG7-dependent non-autophagic pathway plays a critical role in the regulation of neovascularization. In order to gain a better understanding of the non-autophagic pathway-mediated biological functions of the autophagy-associated protein ATG7 and to bring attention to this expanding but understudied research area, this article reviews recent developments in the ATG7-dependent non-autophagic pathways regulating angiogenesis.

show abstract

“…Among them, HIF-1α and HIF-2α are the most extensively characterized and dimerize with HIF-1β respectively, an aryl-hydrocarbon-nuclear receptor translocator (ARNT) [ 28 ]. HIF-1 is a transcriptionally active heterodimer composed of the HIF-1α and HIF-1β subunits [ 29 ]. HIF-1α is localized to cytoplasm and functions as a key transcription factor that regulates the cellular adaptive responses to hypoxia [ 30 ].…”

Section: Overview Of Hif-1αmentioning

confidence: 99%