Glucocorticoid-Beta Regulate B-Adrenergic and Nrf2 via NR4As Productive Pathway For Activating Anti-Inflammation Include Antioxidant Functions and Myocardial Immune Functions
Ashraf Marzouk El Tantawi
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 :-Pro-inflammation +NR4As ¬¬>IL6 ¬>IL17(upon synthase function) ¬¬>activate GCs-beta ¬>¬>B-arrestins¬¬> B Adrenergic ¬¬>Nrf2
synthesis ¬¬>activate ACE functions ¬¬>activate Ang2-AT2 and VEGF-A synthesis ¬¬>anti-inflammatory growth, modulating antioxidative
processes, activating heme oxygenase, and activating B-cell and T-cells functions.
The Inhibition in NR4As productive pathway will inhibit GCs-beta, B-arrestins, B adrenalic and Nrf2 synthesis that will be the main reason for
Atherosclerosis(which can concluded Deficiency in Tph, Glu, and Leu functions).
Also melatonin synthesis which promoted by serotonin(regulated by Tph TGG) protect OPA1 repairs and functions through GTPase synthesis, and
promote NR4As productive pathway for promoting GCs-beta productions and consequently prevent Lipids accumulation by increasing lipolysis
followed by B-arrestins synthesis and Nrf2 productions.
The serotonin roles Is supporting the function of antioxidants through promoting melatonin synthesis(and producing GTPase for OPA1 repairs)
which promote GCs-beta synthesis which activate Nrf2 synthesis via NR4A2 pathway mediated by both B-arrestins, B Adrenergic, which activate
ACE for activating Ang2-AT2 and VEGF-A synthesis for running anti-inflammatory growth.
Where inhibition in melatonin and in Nrf2 function can be the main reason for reducing GTPase functions and the visual memory deficits.
And in conclusion the adoption of oxidative stress will be start by serotonin synthesis which will activate melatonin synthesis that will activate
glucocorticoid-beta synthesis via NR4As pathway then the glucocorticoid-beta will activate B-adrenergic synthesis which will activate Nrf2
production “respectively” :-
The tryptophan "TGG" are necessary for activating serotonin which activate melatonin ¬>that will activate both glutamine synthesis(necessary
for Leu synthesis for Nrf2 synthesis) and glucocorticoid-beta synthesis via NR4As ¬> where NR4As will promote estrogen from 17β-estradiolmediated GPR30 activation ¬>then will activate GCs-beta¬> B-arrestins¬> B(2) -Adrenergic¬> Nrf2 ¬> Ang2-AT2 ¬> VEGF-A ¬> antiinflammatory growth ¬>heme oxygenase ¬¬>adopt antioxidative functions ¬¬>adopté T-cells functions… etc.
Tryptophan(Tph “TGG”) are necessary for modulating oxidative stress and both brain and heart functions through activating serotonin synthesis
which activate melatonin productions, and the Tph is necessary for activating glutamine synthesis which stabilize Nrf2 functions through activating
leucine synthesis.
