Mitochondrial translocation of Nur77 induced by ROS contributed to cardiomyocyte apoptosis in metabolic syndrome

Xu, A; Liu, Jingyi; Liu, Peilin; Jia, Min; Wang, Han; Tao, Ling

doi:10.1016/j.bbrc.2014.03.089

Cited by 19 publications

(8 citation statements)

References 25 publications

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“…NR4A1 translocation is reported to be involved in myocardial ischemia/reperfusion-induced apoptotic injury of cardiac myocytes subjected to metabolic syndrome. 26 It would be interesting to determine whether H 2 O 2 treatment similarly causes cytoplasmic shuttling of NR4A1 in normal fibroblasts. Furthermore, to understand the physiological role of NR4A1 in normal fibroblasts, it is necessary to ascertain whether NR4A1-mediated inhibition of extrinsic apoptosis is specific to HUC-F2 cells or common in normal fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Nuclear receptor subfamily 4, group A, member 1 inhibits extrinsic apoptosis and reduces caspase-8 activity in H₂O₂-induced human HUC-F2 fibroblasts

2014

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Objective: Apoptosis is characterized by distinct morphological and biochemical changes that occur upon activation of a family of serine proteases known as caspases. Reactive oxygen species (ROS) induce apoptosis in many cell systems. Nuclear receptor subfamily 4, group A, member 1 (NR4A1) has been shown to induce apoptosis in a number of cell lineages, but can also paradoxically act as a death inhibitory factor. In the current study, we focused on the potential role of NR4A1 in hydrogen peroxide (H2O2)-induced apoptosis of normal human umbilical cord fibroblast (HUC-F2) cells.Methods: Growth of HUC-F2 cells treated with H2O2 was measured by MTT assay. Analysis of gene expression was performed with a STEP ONE PLUS Real Time PCR system. Inactivation of NR4A1 was treated with siRNA. Apoptosis was measured by Beckman Coulter flow cytometer after inhibition of NR4A1 with siRNA and H2O2 treatment. Caspase -3, -8 and -9 was measured by caspase assay kit.Results: H2O2 treatment led to enhanced NR4A1 expression. Moreover inhibition of NR4A1 with specific siRNA in HUC-F2 cells triggered an increase in apoptosis and caspase-8 and -3 activities following the addition of H2O2.Discussion: Our results collectively suggest that NR4A1 is a regulator that inhibits extrinsic apoptosis in HUC-F2 cells during oxidative stress through reduction of caspase-8 and -3 activities.

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Section: Discussionmentioning

confidence: 99%

Nuclear receptor subfamily 4, group A, member 1 inhibits extrinsic apoptosis and reduces caspase-8 activity in H₂O₂-induced human HUC-F2 fibroblasts

2014

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“…As indicated herein, the ROS level increases in sleep-deprived rats. Previous investigations have confirmed that autophagy can be triggered by oxidative stress to enhance cell survival [41,42].…”

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confidence: 85%

Autophagy Triggered by Oxidative Stress Appears to Be Mediated by the AKT/mTOR Signaling Pathway in the Liver of Sleep-Deprived Rats

Zhang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Sleep deprivation adversely affects the digestive system. Multiple studies have suggested sleep deprivation and oxidative stress are closely related. Autophagy can be triggered by oxidative stress as a self-defense strategy to promote survival. In this study, we investigated the effects of sleep deprivation on liver functions, oxidative stress, and concomitant hepatocyte autophagy, as well as the associated pathways. Enzymatic and nonenzymatic biochemical markers in the serum were used to assess hepatic function and damage. To evaluate the occurrence of autophagy, expression of autophagy-related proteins was tested and autophagosomes were labeled. Additionally, methane dicarboxylic aldehyde (MDA), antioxidant enzymes, and the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway were analyzed using chemical methods and a Western blot. Serum alanine transaminase, aspartate aminotransferase, and alkaline phosphatase increased in sleep-deprived rats. Total protein and albumin abundance was also abnormal. Sleep deprivation induced histopathological changes in the liver. The superoxide dismutase level decreased significantly in the liver of sleep-deprived rats. In contrast, the MDA content increased in the sleep deprivation group. Moreover, the microtubule-associated protein 1 light chain 3 beta (LC3B) II/I ratio and Beclin I content increased considerably in the sleep-deprived rats, while p62 levels decreased. Sleep deprivation apparently inhibited the AKT/mTOR signaling pathway. We conclude that sleep deprivation can induce oxidative stress and ultimately cause liver injury. Autophagy triggered by oxidative stress appears to be mediated by the AKT/mTOR pathway and plays a role in relieving oxidative stress caused by sleep deprivation.

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“…A recent study reported that both histamine and serotonin are pro-angiogenic factors in endothelial cells and in vivo and these effects are dependent on the histamine and serotonin receptors and NR4A1 but are independent of vascular endothelial growth factor (VEGF). These responses are also transitory since after an extended period (10 day), the angiogenesis inhibitor thrombospondin 1 was induced by serotonin and histamine and this response was NR4A1-independent [70]. The role of NR4A1 in inflammation and macrophages will be discussed separately; however, macrophages in areas of plaque formation express NR4A1 [70, 71].…”

Section: Nr4a1 In Cellular Homeostasis and Diseasesmentioning

confidence: 99%

“…These responses are also transitory since after an extended period (10 day), the angiogenesis inhibitor thrombospondin 1 was induced by serotonin and histamine and this response was NR4A1-independent [70]. The role of NR4A1 in inflammation and macrophages will be discussed separately; however, macrophages in areas of plaque formation express NR4A1 [70, 71]. Moreover, in both cell models and ApoE −/− mice maintained on a high fat/cholesterol diet, increased expression of NR4A1 or activation of the receptor by CsnB decreased macrophage derived foam cells and decreased atherosclerotic plaque formation [72].…”

Section: Nr4a1 In Cellular Homeostasis and Diseasesmentioning

confidence: 99%

Nuclear receptor 4A (NR4A) family – orphans no more

Safe

Jin

Morpurgo

et al. 2016

The Journal of Steroid Biochemistry and Molecular Biology

165

161

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The orphan nuclear receptors NR4A1, NR4A2 and NR4A3 are immediate early genes induced by multiple stressors, and the NR4A1 receptors play an important role in maintaining cellular homeostasis and disease. There is increasing evidence for the role of these receptors in metabolic, cardiovascular and neurological functions and also in inflammation and inflammatory diseases and in immune functions and cancer. Despite the similarities of NR4A1, NR4A2 and NR4A3 and their interactions with common cis-genomic elements, they exhibit unique activities and cell-/tissue-specific functions. Although endogenous ligands for NR4A receptors have not been identified, there is increasing evidence that structurally-diverse synthetic molecules can directly interact with the ligand binding domain of NR4A1 and act as agonists or antagonists, and ligands for NR4A2 and NR4A3 have also been identified. Since NR4A receptors are key factors in multiple diseases, there are opportunities for the future development of NR4A ligands for clinical applications in treating multiple health problems including metabolic, neurologic and cardiovascular diseases, other inflammatory conditions, and cancer.

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Mitochondrial translocation of Nur77 induced by ROS contributed to cardiomyocyte apoptosis in metabolic syndrome

Cited by 19 publications

References 25 publications

Nuclear receptor subfamily 4, group A, member 1 inhibits extrinsic apoptosis and reduces caspase-8 activity in H₂O₂-induced human HUC-F2 fibroblasts

Nuclear receptor subfamily 4, group A, member 1 inhibits extrinsic apoptosis and reduces caspase-8 activity in H₂O₂-induced human HUC-F2 fibroblasts

Autophagy Triggered by Oxidative Stress Appears to Be Mediated by the AKT/mTOR Signaling Pathway in the Liver of Sleep-Deprived Rats

Nuclear receptor 4A (NR4A) family – orphans no more

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Mitochondrial translocation of Nur77 induced by ROS contributed to cardiomyocyte apoptosis in metabolic syndrome

Cited by 19 publications

References 25 publications

Nuclear receptor subfamily 4, group A, member 1 inhibits extrinsic apoptosis and reduces caspase-8 activity in H2O2-induced human HUC-F2 fibroblasts

Nuclear receptor subfamily 4, group A, member 1 inhibits extrinsic apoptosis and reduces caspase-8 activity in H2O2-induced human HUC-F2 fibroblasts

Autophagy Triggered by Oxidative Stress Appears to Be Mediated by the AKT/mTOR Signaling Pathway in the Liver of Sleep-Deprived Rats

Nuclear receptor 4A (NR4A) family – orphans no more

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Nuclear receptor subfamily 4, group A, member 1 inhibits extrinsic apoptosis and reduces caspase-8 activity in H₂O₂-induced human HUC-F2 fibroblasts

Nuclear receptor subfamily 4, group A, member 1 inhibits extrinsic apoptosis and reduces caspase-8 activity in H₂O₂-induced human HUC-F2 fibroblasts