scholarly journals Effects of NRF-1 and PGC-1α Cooperation on HIF-1α and Rat Cardiomyocyte Apoptosis Under Hypoxia

2021 ◽  
Author(s):  
Nan Niu ◽  
Hui Li ◽  
Xiancai Du ◽  
Chan Wang ◽  
Junliang Li ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Regulatory Elements ◽  
Cardiomyocyte Apoptosis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Rat Cardiomyocytes ◽  
Nuclear Respiratory Factor ◽  
Transcriptional Regulatory Elements ◽  
Nuclear Respiratory Factor 1 ◽  
Myocardial Hypoxia

Abstract Background: Hypoxia is a primary inducer of cardiomyocyte injury, its significant marker being hypoxia-induced cardiomyocyte apoptosis. Nuclear respiratory factor-1 (NRF-1) and hypoxia-inducible factor-1α (HIF-1α) are transcriptional regulatory elements implicated in multiple biological functions, including oxidative stress response. However, their roles in hypoxia-induced cardiomyocyte apoptosis remain unknown. The effect HIF-α, together with NRF-1, exerts on cardiomyocyte apoptosis also remains unclear. Methods: We established a myocardial hypoxia model and investigated the effects of these proteins on the proliferation and apoptosis of rat cardiomyocytes (H9C2) under hypoxia. Further, we examined the association between NRF-1 and HIF-1α to improve the current understanding of NRF-1 anti-apoptotic mechanisms. Results: The results show that NRF-1 and HIF-1α are important anti-apoptotic molecules in H9C2 cells under hypoxia, although their regulatory mechanisms differ. NRF-1 could bind to the promoter region of Hif1a and negatively regulate its expression. Additionally, HIF-1β exhibited competitive binding with NRF-1 and HIF-1α, demonstrating a synergism between NRF-1 and the peroxisome proliferator-activated receptor-gamma coactivator-1α. Conclusion: These results indicate that cardiomyocytes can regulate different molecular patterns to tolerate hypoxia, providing a novel methodological framework for studying cardiomyocyte apoptosis under hypoxia.

scholarly journals Effects of NRF-1 and PGC-1α Cooperation on HIF-1α and Rat Cardiomyocyte Apoptosis Under Hypoxia

2021 ◽  
Author(s):  
Nan Niu ◽  
Hui Li ◽  
Xiancai Du ◽  
Chan Wang ◽  
Junliang Li ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Regulatory Elements ◽  
Cardiomyocyte Apoptosis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Rat Cardiomyocytes ◽  
Nuclear Respiratory Factor ◽  
Transcriptional Regulatory Elements ◽  
Nuclear Respiratory Factor 1 ◽  
Myocardial Hypoxia

Abstract Hypoxia is a primary inducer of cardiomyocyte injury, its significant marker being hypoxia-induced cardiomyocyte apoptosis. Nuclear respiratory factor-1 (NRF-1) and hypoxia-inducible factor (HIF)-1α are transcriptional regulatory elements implicated in multiple biological functions, including oxidative stress response. However, their roles in hypoxia-induced cardiomyocyte apoptosis remain unknown. The effect HIF-α, together with NRF-1, exerts on cardiomyocyte apoptosis also remains unclear. We established a myocardial hypoxia model and investigated the effects of these proteins on the proliferation and apoptosis of rat cardiomyocytes (H9C2) under hypoxia. Further, we examined the association between NRF-1 and HIF-1α to improve the current understanding of NRF-1 anti-apoptotic mechanisms. The results showed that NRF-1 and HIF-1α are important anti-apoptotic molecules in H9C2 cells under hypoxia, although their regulatory mechanisms differ. NRF-1 could bind to the promoter region of Hif-1α and negatively regulate its expression. Additionally, HIF-1β exhibited competitive binding with NRF-1 and HIF-1α, demonstrating a synergism between NRF-1 and the peroxisome proliferator-activated receptor-gamma coactivator-1α. These results indicate that cardiomyocytes can regulate different molecular patterns to tolerate hypoxia, providing a novel methodological framework for studying cardiomyocyte apoptosis under hypoxia.

scholarly journals Effects of NRF-1 and PGC-1α Cooperation on HIF-1α and Rat Cardiomyocyte Apoptosis Under Hypoxia

2021 ◽  
Author(s):  
Nan Niu ◽  
Hui Li ◽  
Xiancai Du ◽  
Chan Wang ◽  
Junliang Li ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Regulatory Elements ◽  
Cardiomyocyte Apoptosis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Rat Cardiomyocytes ◽  
Nuclear Respiratory Factor ◽  
Transcriptional Regulatory Elements ◽  
Nuclear Respiratory Factor 1 ◽  
Myocardial Hypoxia

Abstract Hypoxia is a primary inducer of cardiomyocyte injury, its significant marker being hypoxia-induced cardiomyocyte apoptosis. Nuclear respiratory factor-1 (NRF-1) and hypoxia-inducible factor (HIF)-1α are transcriptional regulatory elements implicated in multiple biological functions, including oxidative stress response. However, their roles in hypoxia-induced cardiomyocyte apoptosis remain unknown. The effect HIF-α, together with NRF-1, exerts on cardiomyocyte apoptosis also remains unclear. We established a myocardial hypoxia model and investigated the effects of these proteins on the proliferation and apoptosis of rat cardiomyocytes (H9C2) under hypoxia. Further, we examined the association between NRF-1 and HIF-1α to improve the current understanding of NRF-1 anti-apoptotic mechanisms. The results showed that NRF-1 and HIF-1α are important anti-apoptotic molecules in H9C2 cells under hypoxia, although their regulatory mechanisms differ. NRF-1 could bind to the promoter region of Hif-1α and negatively regulate its expression. Additionally, HIF-1β exhibited competitive binding with NRF-1 and HIF-1α, demonstrating a synergism between NRF-1 and the peroxisome proliferator-activated receptor-gamma coactivator-1α. These results indicate that cardiomyocytes can regulate different molecular patterns to tolerate hypoxia, providing a novel methodological framework for studying cardiomyocyte apoptosis under hypoxia.

scholarly journals Effects of NRF-1 and PGC-1α Cooperation on HIF-1α and Rat Cardiomyocyte Apoptosis Under Hypoxia

2022 ◽  
Author(s):  
Nan Niu ◽  
Hui Li ◽  
Xiancai Du ◽  
Chan Wang ◽  
Junliang Li ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Regulatory Elements ◽  
Cardiomyocyte Apoptosis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Rat Cardiomyocytes ◽  
Nuclear Respiratory Factor ◽  
Transcriptional Regulatory Elements ◽  
Nuclear Respiratory Factor 1 ◽  
Myocardial Hypoxia

Abstract Hypoxia is a primary inducer of cardiomyocyte injury, its significant marker being hypoxia-induced cardiomyocyte apoptosis. Nuclear respiratory factor-1 (NRF-1) and hypoxia-inducible factor (HIF)-1α are transcriptional regulatory elements implicated in multiple biological functions, including oxidative stress response. However, their roles in hypoxia-induced cardiomyocyte apoptosis remain unknown. The effect HIF-α, together with NRF-1, exerts on cardiomyocyte apoptosis also remains unclear. We established a myocardial hypoxia model and investigated the effects of these proteins on the proliferation and apoptosis of rat cardiomyocytes (H9C2) under hypoxia. Further, we examined the association between NRF-1 and HIF-1α to improve the current understanding of NRF-1 anti-apoptotic mechanisms. The results showed that NRF-1 and HIF-1α are important anti-apoptotic molecules in H9C2 cells under hypoxia, although their regulatory mechanisms differ. NRF-1 could bind to the promoter region of Hif-1α and negatively regulate its expression. Additionally, HIF-1β exhibited competitive binding with NRF-1 and HIF-1α, demonstrating a synergism between NRF-1 and the peroxisome proliferator-activated receptor-gamma coactivator-1α. These results indicate that cardiomyocytes can regulate different molecular patterns to tolerate hypoxia, providing a novel methodological framework for studying cardiomyocyte apoptosis under hypoxia.

Beneficial Effect of Flavone Derivatives on Aβ-Induced Memory Deficit Is Mediated by Peroxisome Proliferator-Activated Receptor γ Coactivator 1α

2015 ◽  
Vol 34 (3) ◽  
pp. 274-283 ◽  
Author(s):  
Farshad Arsalandeh ◽  
Shahin Ahmadian ◽  
Forough Foolad ◽  
Fariba Khodagholi ◽  
Mahdi M. Farimani ◽  
...  
Keyword(s):  
Mitochondrial Biogenesis ◽  
Neuroprotective Effect ◽  
Memory Function ◽  
Adenosine Monophosphate ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Respiratory Factor ◽  
Mitochondrial Transcription Factor ◽  
Nuclear Respiratory Factor 1

In the present study, the neuroprotective effect of 5-hydroxy-6,7,4′-trimethoxyflavone (flavone 1), a natural flavone, was investigated in comparison with another flavone, 5,7,4′-trihydroxyflavone (flavone 2) on the hippocampus of amyloid beta (Aβ)-injected rats. Rats were treated with the 2 flavones (1 mg/kg/d) for 1 week before Aβ injection. Seven days after Aβ administration, memory function of rats was assessed in a passive avoidance test (PAT). Changes in the levels of mitochondrial transcription factor A (TFAM), peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α), phospho-adenosine monophosphate (AMP)-activated protein kinase (pAMPK), AMPK, phospho-cAMP-responsive element-binding protein (CREB), CREB, and nuclear respiratory factor 1 (NRF-1) proteins were determined by Western blot analysis. Our results showed an improvement in memory in rats pretreated with flavonoids. At the molecular level, phosphorylation of CREB, known as the master modulator of memory processes, increased. On the other hand, the level of mitochondrial biogenesis factors, PGC-1α and its downstream molecules NRF-1 and TFAM significantly increased by dietary administration of 2 flavones. In addition, flavone 1 and flavone 2 prevented mitochondrial swelling and mitochondrial membrane potential reduction. Our results provided evidence that flavone 1 is more effective than flavone 2 presumably due to its O-methylated groups. In conclusion, it seems that in addition to classical antioxidant effect, flavones exert part of their protective effects through mitochondrial biogenesis.

Activation of SIRT1 Alleviates Mitochondrial Dysfunction in The Trigeminal Nucleus Caudalis in a Rat Model of Chronic Migraine

2020 ◽  
Author(s):  
jie liang ◽  
xue zhou ◽  
jiang wang ◽  
zhaoyang fei ◽  
guangcheng qin ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Chronic Migraine ◽  
Rat Model ◽  
Vital Role ◽  
Peroxisome Proliferator ◽  
Trigeminal Nucleus ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Respiratory Factor ◽  
Trigeminal Nucleus Caudalis ◽  
Nuclear Respiratory Factor 1

Abstract Background: The mechanism of chronic migraine (CM) is still unclear and mitochondrial dysfunction plays a possible role in migraine pathophysiology. Silent information regulator 1 (SIRT1) plays a vital role in mitochondrial dysfunction in many diseases, but there is no information about SIRT1 in CM.The aim of this study was to explore the role of SIRT1 in mitochondrial dysfunction in CM. Methods： A rat model was established through repeated dural infusions of inflammatory soup (IS) for seven days to simulate CM attacks. Cutaneous hyperalgesia caused by the repeated infusions of IS was detected using the von Frey test. Then, we detected SIRT1 expression in the trigeminal nucleus caudalis (TNC). To explore the effect of SIRT1 on mitochondrial dysfunction in CM rats, we examined whether SRT1720, an activator of SIRT1, altered mitochondrial dysfunction in CM rats. Results： Repeated infusions of IS resulted in cutaneous hyperalgesia accompanied bydownregulation of SIRT1.SRT1720 significantly alleviated the cutaneous hyperalgesia induced by repeated infusions of IS. Furthermore, activation of SIRT1 markedly increased the expression of peroxisome proliferator-activated receptor gamma-coactivator 1-alpha(PGC-1α), transcription factor A (TFAM), nuclear respiratory factor 1 (NRF-1), and nuclear respiratory factor 2(NRF-2) mitochondrial DNA (mtDNA) and increased the ATP content and mitochondrial membrane potential. Conclusions ：Our results indicate that SIRT1 may have an effect on mitochondrial dysfunction in CM rats. Activation of SIRT1 has a protective effect on mitochondrial function in CM rats.

scholarly journals Telomeric injury by KML001 in human T cells induces mitochondrial dysfunction through the p53-PGC-1α pathway

2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Madison Schank ◽  
Juan Zhao ◽  
Ling Wang ◽  
Zhengke Li ◽  
Dechao Cao ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mitochondrial Dysfunction ◽  
Cell Aging ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Respiratory Factor ◽  
Nuclear Respiratory Factor 1 ◽  
Human T Cell ◽  
Wide Range

AbstractTelomere erosion and mitochondrial dysfunction are prominent features of aging cells with progressive declines of cellular functions. Whether telomere injury induces mitochondrial dysfunction in human T lymphocytes, the major component of adaptive host immunity against infection and malignancy, remains unclear. We have recently shown that disruption of telomere integrity by KML001, a telomere-targeting drug, induces T cell senescence and apoptosis via the telomeric DNA damage response (DDR). In this study, we used KML001 to further investigate the role and mechanism of telomere injury in mitochondrial dysregulation in aging T cells. We demonstrate that targeting telomeres by KML001 induces mitochondrial dysfunction, as evidenced by increased mitochondrial swelling and decreased mitochondrial membrane potential, oxidative phosphorylation, mitochondrial DNA content, mitochondrial respiration, oxygen consumption, glycolysis, and ATP energy production. Mechanistically, we found that the KML001-induced telomeric DDR activated p53 signaling, which in turn repressed the expression of peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) and nuclear respiratory factor 1 (NRF-1), leading to T cell mitochondrial dysfunction. These results, forging a direct link between telomeric and mitochondrial biology, shed new light on the human T cell aging network, and demonstrate that the p53-PGC-1α-NRF-1 axis contributes to mitochondrial dysfunction in the setting of telomeric DDR. This study suggests that targeting this axis may offer an alternative, novel approach to prevent telomere damage-mediated mitochondrial and T cell dysfunctions to combat a wide range of immune aging-associated human diseases.

scholarly journals Rhein Relieves Oxidative Stress in an Aβ1-42 Oligomer-Burdened Neuron Model by Activating the SIRT1/PGC-1α-Regulated Mitochondrial Biogenesis

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhihui Yin ◽  
Xinyue Geng ◽  
Zhengyi Zhang ◽  
Ying Wang ◽  
Xiaoyan Gao
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Biogenesis ◽  
Antioxidant Defense System ◽  
Sirtuin 1 ◽  
Early Event ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mitochondrial Oxidative Stress ◽  
Nuclear Respiratory Factor ◽  
Nuclear Respiratory Factor 1

Neuronal mitochondrial oxidative stress induced by β-amyloid (Aβ) is an early event of Alzheimer’s disease (AD). Emerging evidence has shown that antioxidant therapy represents a promising therapeutic strategy for the treatment of AD. In this study, we investigated the antioxidant activity of rhein against Aβ1-42 oligomer-induced mitochondrial oxidative stress in primary neurons and proposed a potential antioxidant pathway involved. The results suggested that rhein significantly reduced reactive oxygen species (ROS) level, reversed the depletion of mitochondrial membrane potential, and protected neurons from oxidative stress-associated apoptosis. Moreover, further study indicated that rhein activated mitochondrial biogenesis accompanied by increased cytochrome C oxidase (CytOx) and superoxide dismutase (SOD) activities. CytOx on the respiratory chain inhibited the production of ROS from electron leakage and SOD helped to eliminate excess ROS. Finally, western blot analysis confirmed that rhein remarkedly increased the protein expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) together with its upstream deacetylase sirtuin 1 (SIRT1), and activated downstream transcription factor nuclear respiratory factor 1, promoting mitochondrial biogenesis. In conclusion, our results demonstrate that rhein activates mitochondrial biogenesis regulated by the SIRT1/PGC-1α pathway as an antioxidant defense system against Aβ1-42 oligomer-induced oxidative stress. These findings broaden our knowledge of improving mitochondrial biogenesis as an approach for relieving neuronal oxidative stress in AD.

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