NR4A1 promotes oxidative stresses after myocardial ischemia reperfusion injury in aged mice

Xue, Peng; Wang, Wen‐Juan; Wang, Wenhao; Qi, Jingrui

doi:10.1016/j.exger.2022.111742

“…And it has been revealed that: The Regulation of mitochondrial oxidative stress by B-arrestins in cardiovascular fibroblast [37]. That the same mechanism that mentioned previously of tryptophan function for modulating antioxidative stress can be done in cardiovascular fibroblast by B-arrestins and will be done in bone marrow during activating stem cells functions and bone growth mediated by both B-adrenergic and Nrf2 productive functions too.…”

Section: The β2-adrenergic Receptor (β2-ar) Produced By Nr4as Pathway...mentioning

confidence: 77%

GCs-beta and B-arrestins Regulate Nrf2 via NR4As Productive Pathway Mediated by B-adrenergic for Anti-inflammation and Adopting Myocardial and Immune Functions

Tantawi¹

2023

Jap J Clin & Med Res

1

0

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The nuclear receptors “NR4As” productive pathway is the so important pathways for activating classic estrogen receptors and are important for regulating the adopted cellular anti-inflammatory growth (mediated by glucocorticoids, Nrf2, Ang2-AT2, and VEGF-A synthesis)which considered as the basic for B-arrestins synthesis which adopt B Adrenergic, and Nrf2 synthesis, that Nrf2 is strong activator to ACE functions for promoting Ang2-AT2 and VEGF-A synthesis for running the adopted anti-inflammatory growth and heme oxygenase. The modulation of oxidative stress will be done by serotonin synthesis (regulated by tryptophan “TGG”) which will promote melatonin synthesis which necessary to activate glucocorticoids productions via NR4A2 pathway followed by B-arrestins and Nrf2 productions for activating Ang2-AT2 and VEGF-A productions. That melatonin synthesis will be associated with GTPase production which promote and activate OPA1 repairs and functions, and responsible for activating glutamine synthesis which stabilize Leu functions through Nrf2 functions. This study concluded that NR4As productive pathway are the important pathway for improving anti-oxidation through improving IL6 productivity to IL17 productions, and is important for glucocorticoids-beta synthesis followed by B-arrestins productions which activate B Adrenergic synthesis that are necessary for activating Nrf2 production that followed by activating ACE for Ang2-AT2 and VEGF-A synthesis for running anti-inflammatory growth, modulating antioxidative stress, activate heme oxygenase, modulating brain function and memories growth , and activating T-cells and B-cell functions. That NR4As exert multilevel regulations of brain function and cardiac functions that protect immune survival from vascular cardiac diseases, and are the primary modulator to pro-inflammation and stimulator for variety of active genes and subunits started by estrogen and GCs-beta productions which followed by activating B-arrestins which activate B Adrenergic synthesis which has the roles of activating Nrf2 productions for adopting antioxidative functions, heme oxygenase, vasoconstriction functions, and anti-inflammatory growth mediated by Ang2-AT2 and VEGF-A synthesis.

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“…And the Regulation of oxidative stress can started firstly by serotonin followed by melatonin synthesis for activating NR4A2 pathway for GCs-beta synthesis which will regulate B-arrestins synthesis for promoting firstly Beta(2)-adrenergic followed by Nrf2 productions which will modulate the oxidative stress and will activate Ang2-AT2 and VEGF-A synthesis(by activating ACE functions) for activating anti-inflammatory growth. That , NR4A1 promotes oxidative stresses after myocardial ischemia reperfusion injury [39].…”

Section: How Regulation Of Mitochondrial Oxidative Functions Done By ...mentioning

confidence: 99%

Glucocorticoid-Beta Regulate B-Adrenergic and Nrf2 via NR4As Productive Pathway For Activating Anti-Inflammation Include Antioxidant Functions and Myocardial Immune Functions

Tantawi¹

2023

Med Clin Sci

0

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The nuclear receptors “NR4As” productive pathway is the so important pathways for activating classic estrogen receptors and are important for regulating the adopted cellular anti-inflammatory growth(mediated by glucocorticoids, Nrf2, Ang2-AT2, and VEGF-A synthesis) which considered as the basic for B-arrestins synthesis which adopt B Adrenergic, and Nrf2 synthesis, that Nrf2 is strong activator to ACE functions for promoting Ang2-AT2 and VEGF-A synthesis for running the adopted anti-inflammatory growth and heme oxygenase. The modulation of oxidative stress will be done by serotonin synthesis(regulated by tryptophan “TGG”) which will promote melatonin synthesis which necessary to activate glucocorticoids productions via NR4A2 pathway followed by B-arrestins and Nrf2 productions for activating Ang2-AT2 and VEGF-A productions. That melatonin synthesis will be associated with GTPase production which promote and activate OPA1 repairs and functions , and responsible for activating glutamine synthesis which stabilize Leucine functions through Nrf2 functions. This study concluded that NR4As productive pathway are the important pathway for improving antioxidation through improving IL6 productivity to IL17 productions, and is important for glucocorticoidsbeta synthesis followed by B-arrestins productions which activate B Adrenergic synthesis that are necessary for activating Nrf2 production that followed by activating ACE for Ang2-AT2 and VEGF-A synthesis for running anti-inflammatory growth, modulating antioxidative stress, activate heme oxygenase, modulating brain function and memories growth , and activating T-cells and B-cell functions. That NR4As exert multilevel regulations of brain function and cardiac functions that protect immune survival from vascular cardiac diseases, and are the primary modulator to pro-inflammation and stimulator for variety of active genes and subunits started by estrogen and GCs-beta productions which followed by activating B-arrestins which activate B Adrenergic synthesis which has the roles of activating Nrf2 productions for adopting antioxidative functions, heme oxygenase, vasoconstriction functions, and anti-inflammatory growth mediated by Ang2-AT2 and VEGF-A synthesis. NR4As pathway has the role of improving cytokines which produced by cDC2s for producing IL6 which improved to IL17 synthesis(upon synthase function and availability of glutamine for supporting Leu synthesis and functions) which necessary for modulating GCs-beta synthesis followed by both B-arrestins synthesis and B Adrenergic then followed by Nrf2 productions,(note ‘N-Acetyl Serotonin activate Nuclear Factor Erythroid 2-Related Factor 2 for Alleviating Oxidative Damage mediated through promoting glutamine synthesis for activating Leu necessary for Nrf2 functions) then followed by activating Ang2-AT2 and VEGF-A necessary for anti-inflammatory growth for T cell functions and B-cell functions(that MZ B-cells which characterized by NR4As expression possess a strong B-cell regulatory functions are the main activator to glucocorticoids, to B-arrestins, and to Nrf2 production for activating Ang2-AT2 and VEGF-A synthesis). Also, this study concluded that β3-adrenergic receptors has important roles for preventing myocardial fibrosis by modulating antioxidative function through activating Nrf2 synthesis that B-adrenergic regulated by B-arrestins via NR4As productive pathway for activating Nrf2 production, that NR4As is a very important pathway for modulating oxidative stress(starred by the stimulation and modulation by serotonin followed by melatonin) for protecting heart, brain and liver functions from oxidative damages and from irregular proliferation activities. Also the β3-adrenergic responsible for lipolysis , and has the role of adoptung both anti-inflammatory growth and antioxidstive processes through activating Nrf2 synthesis followed by activating Ang2-AT2 and VEGF-A productions via NR4As productive pathway(where NRF2’s has imp role is modulating stress response that can now be revised to be included the regulation of the basic functions of stem cells) , that NR4A2 pathway can be concluded to :-

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“…In brain microvascular endothelial cells, lipopolysaccharide increases the expression of circ0057583/NR4A1. Additionally, LPSinduced hBMEC injury is attenuated by inducing cell proliferation and angiogenesis and inhibiting apoptosis, autophagy, and in ammation once their expressions are inhibited [39] . The above ndings suggest that NR4A1 is a key mediator in the regulation of in ammation and that NR4A1 may be a potential therapeutic target for in ammation-related diseases.…”

Section: Nr4a1 In In Ammationmentioning

confidence: 99%

“…NR4A1 interferes with cardiac microvascular ischemia reperfusion injury by triggering mitochondrial apoptosis [61] . Furthermore, NR4A1 also induces myocardial infarction through oxidative stress and exacerbates cardiac injury during myocardial infarction [39] . However, a study by Ji et al showed that NR4A1 activation inhibits cardiac brosis by regulating glycolysis in a myocardial infarction rat model [62] .…”

Section: Nr4a1 In Cardiovascular Diseasementioning

confidence: 99%