scholarly journals Retinoid X receptor activation reverses age-related deficiencies in myelin debris phagocytosis and remyelination

Brain ◽  
2015 ◽  
Vol 138 (12) ◽  
pp. 3581-3597 ◽  
Author(s):  
Muktha S. Natrajan ◽  
Alerie G. de la Fuente ◽  
Abbe H. Crawford ◽  
Eimear Linehan ◽  
Vanessa Nuñez ◽  
...  
Keyword(s):  
Receptor Activation ◽  
Retinoid X Receptor ◽  
Age Related ◽  
Myelin Debris

Age-related vulnerability to nigral dopaminergic degeneration in rats via Zn2+-permeable GluR2-lacking AMPA receptor activation

2021 ◽  
Vol 83 ◽  
pp. 69-76
Author(s):  
Satoko Nakajima ◽  
Nana Saeki ◽  
Haruna Tamano ◽  
Ryusuke Nishio ◽  
Misa Katahira ◽  
...  
Keyword(s):  
Ampa Receptor ◽  
Receptor Activation ◽  
Age Related ◽  
Dopaminergic Degeneration

scholarly journals Reversal of age-related oxidative stress prevents hippocampal synaptic plasticity deficits by protecting d-serine-dependent NMDA receptor activation

Aging Cell ◽  
2012 ◽  
Vol 11 (2) ◽  
pp. 336-344 ◽  
Author(s):  
Coline Haxaire ◽  
Fabrice R Turpin ◽  
Brigitte Potier ◽  
Myriam Kervern ◽  
Pierre-Marie Sinet ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Receptor Activation ◽  
Hippocampal Synaptic Plasticity ◽  
Age Related ◽  
Nmda Receptor Activation

scholarly journals Retinoid X receptor activation is essential for docosahexaenoic acid protection of retina photoreceptors

2013 ◽  
Vol 54 (8) ◽  
pp. 2236-2246 ◽  
Author(s):  
Olga L. German ◽  
Sandra Monaco ◽  
Daniela L. Agnolazza ◽  
Nora P. Rotstein ◽  
Luis E. Politi
Keyword(s):  
Docosahexaenoic Acid ◽  
Receptor Activation ◽  
Retinoid X Receptor

scholarly journals Perivascular Adipose Tissue-Enhanced Vasodilation in Metabolic Syndrome Rats by Apelin and N-Acetyl–l-Cysteine-Sensitive Factor(s)

2018 ◽  
Vol 20 (1) ◽  
pp. 106 ◽  
Author(s):  
Satomi Kagota ◽  
Kana Maruyama-Fumoto ◽  
Saki Iwata ◽  
Miho Shimari ◽  
Shiori Koyanagi ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Mrna Level ◽  
Receptor Activation ◽  
At1 Receptor ◽  
Mesenteric Arteries ◽  
Mrna Levels ◽  
Perivascular Adipose Tissue ◽  
Age Related ◽  
Sensitive Factor

Perivascular adipose tissue (PVAT) can regulate vascular tone. In mesenteric arteries of SHRSP.Z-Leprfa/IzmDmcr rats (SHRSP.ZF) with metabolic syndrome, vascular dysfunction is compensated by PVAT-dependent mechanisms that disappear with increasing age. In this study, we investigated the mechanisms of the age-related changes and responsible factor(s) involved in the enhancing effects of mesenteric arterial PVAT in SHRSP.ZF. Acetylcholine- and sodium nitroprusside-induced relaxations of isolated arteries were greater with PVAT than without PVAT at 17 and 20 weeks of age (wks), and as expected, this enhancement by the presence of PVAT disappeared at 23 wks. PVAT mRNA levels of angiotensin II type 1 (AT1) receptor-associated protein was less and AT1 receptor was unchanged at 23 wks when compared to 20 wks. At 20 wks, the enhanced acetylcholine-induced relaxation by the presence of PVAT was inhibited by N-acetyl-l-cysteine (NAC). Acetylcholine-induced relaxation of arteries without PVAT was increased in the presence of exogenously added apelin. PVAT mRNA level of apelin was higher in SHRSP.ZF than in control Wistar-Kyoto rats, and the level was decreased with aging. These results suggest that AT1 receptor activation in PVAT, and changes in the regulation of apelin and a NAC-sensitive factor are related to the age-dependent deterioration of the vasodilation enhancing effects of mesenteric arterial PVAT in SHRSP.ZF.

scholarly journals Retinoid X Receptor (RXR) Agonist-Induced Activation of Dominant-Negative RXR-Retinoic Acid Receptor α403 Heterodimers Is Developmentally Regulated during Myeloid Differentiation

1999 ◽  
Vol 19 (5) ◽  
pp. 3372-3382 ◽  
Author(s):  
Barton S. Johnson ◽  
Roshantha A. S. Chandraratna ◽  
Richard A. Heyman ◽  
Elizabeth A. Allegretto ◽  
LeMoyne Mueller ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Trichostatin A ◽  
Receptor Activation ◽  
Nuclear Hormone Receptor ◽  
Retinoid X Receptor ◽  
Dominant Negative ◽  
Mouse Bone Marrow ◽  
Granulocytic Differentiation ◽  
Response Elements ◽  
Dominant Negative Activity

ABSTRACT The multiple biologic activities of retinoic acid (RA) are mediated through RAR and retinoid X receptor (RXR) nuclear receptors that interact with specific DNA target sequences as heterodimers (RXR-RAR) or homodimers (RXR-RXR). RA receptor activation appears critical to regulating important aspects of hematopoiesis, since transducing a COOH-terminally truncated RARα exhibiting dominant-negative activity (RARα403) into normal mouse bone marrow generates hematopoietic growth factor-dependent cell lines frozen at the multipotent progenitor (EML) or committed promyelocyte (MPRO) stages. Nevertheless, relatively high, pharmacological concentrations of RA (1 to 10 μM) overcome these differentiation blocks and induce terminal granulocytic differentiation of the MPRO promyelocytes while potentiating interleukin-3 (IL-3)-induced commitment of EML cells to the granulocyte/monocyte lineage. In the present study, we utilized RXR- and RAR-specific agonists and antagonists to determine how RA overcomes the dominant-negative activity of the truncated RARα in these different myeloid developmental stages. Unexpectedly, we observed that an RXR-specific, rather than an RAR-specific, agonist induces terminal granulocytic differentiation of MPRO promyelocytes, and this differentiation is associated with activation of DNA response elements corresponding to RAR-RXR heterodimers rather than RXR-RXR homodimers. This RXR agonist activity is blocked by RAR-specific antagonists, suggesting extensive cross-talk between the partners of the RXR-RARα403 heterodimer. In contrast, in the more immature, multipotent EML cells we observed that this RXR-specific agonist is inactive either in potentiating IL-3-mediated commitment of EML cells to the granulocyte lineage or in transactivating RAR-RXR response elements. RA-triggered GALdbd-RARα hybrid activity in these cells indicates that the multipotent EML cells harbor substantial nuclear hormone receptor coactivator activity. However, the histone deacetylase (HDAC) inhibitor trichostatin A readily activates an RXR-RAR reporter construct in the multipotent EML cells but not in the committed MPRO promyelocytes, indicating that differences in HDAC-containing repressor complexes in these two closely related but distinct hematopoietic lineages might account for the differential activation of the RXR-RARα403 heterodimers that we observed at these different stages of myeloid development.

scholarly journals Intake of Products Containing Anthocyanins, Flavanols, and Flavanones, and Cognitive Function: A Narrative Review

2021 ◽  
Vol 13 ◽  
Author(s):  
Samantha L. Gardener ◽  
Stephanie R. Rainey-Smith ◽  
Michael Weinborn ◽  
Catherine P. Bondonno ◽  
Ralph N. Martins
Keyword(s):  
Cognitive Function ◽  
Intracellular Signaling ◽  
Healthy Aging ◽  
Receptor Activation ◽  
Cognitive Outcomes ◽  
Future Research ◽  
Aging Brain ◽  
Dietary Interventions ◽  
Intracellular Signaling Pathway ◽  
Age Related

The purpose of this review is to examine human research studies published within the past 6 years which evaluate the role of anthocyanin, flavanol, and flavanone consumption in cognitive function, and to discuss potential mechanisms of action underlying any observed benefits. Evidence to date suggests the consumption of flavonoid-rich foods, such as berries and cocoa, may have the potential to limit, or even reverse, age-related declines in cognition. Over the last 6 years, the flavonoid subgroups of anthocyanins, flavanols, and flavanones have been shown to be beneficial in terms of conferring neuroprotection. The mechanisms by which flavonoids positively modulate cognitive function are yet to be fully elucidated. Postulated mechanisms include both direct actions such as receptor activation, neurotrophin release and intracellular signaling pathway modulation, and indirect actions such as enhancement of cerebral blood flow. Further intervention studies conducted in diverse populations with sufficient sample sizes and long durations are required to examine the effect of consumption of flavonoid groups on clinically relevant cognitive outcomes. As populations continue to focus on adopting healthy aging strategies, dietary interventions with flavonoids remains a promising avenue for future research. However, many questions are still to be answered, including identifying appropriate dosage, timeframes for intake, as well as the best form of flavonoids, before definitive conclusions can be drawn about the extent to which their consumption can protect the aging brain.

scholarly journals DP1 Activation Reverses Age-Related Hypertension Via NEDD4L-Mediated T-Bet Degradation in T Cells

Circulation ◽  
2020 ◽  
Vol 141 (8) ◽  
pp. 655-666
Author(s):  
Deping Kong ◽  
Qiangyou Wan ◽  
Juanjuan Li ◽  
Shengkai Zuo ◽  
Guizhu Liu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
T Cells ◽  
T Cell ◽  
Receptor Activation ◽  
Superoxide Production ◽  
Cytokine Secretion ◽  
Male Mice ◽  
Blood Pressure Elevation ◽  
Age Related ◽  
Th1 Cytokine

Background: Blood pressure often rises with aging, but exact mechanisms are still not completely understood. With aging, the level of proinflammatory cytokines increases in T lymphocytes. Prostaglandin D 2 , a proresolution mediator, suppresses Type 1 T helper (Th1) cytokines through D-prostanoid receptor 1 (DP1). In this study, we aimed to investigate the role of the prostaglandin D 2 /DP1 axis in T cells on age-related hypertension. Methods: To clarify the physiological and pathophysiological roles of DP1 in T cells with aging, peripheral blood samples were collected from young and older male participants, and CD4 + T cells were sorted for gene expression, prostaglandin production, and Western blot assays. Mice blood pressure was quantified by invasive telemetric monitor. Results: The prostaglandin D 2 /DP1 axis was downregulated in CD4 + T cells from older humans and aged mice. DP1 deletion in CD4 + T cells augmented age-related hypertension in aged male mice by enhancing Th1 cytokine secretion, vascular remodeling, CD4 + T cells infiltration, and superoxide production in vasculature and kidneys. Conversely, forced expression of exogenous DP1 in T cells retarded age-associated hypertension in mice by reducing Th1 cytokine secretion. Tumor necrosis factor α neutralization or interferon γ deletion ameliorated the age-related hypertension in DP1 deletion in CD4 + T cells mice. Mechanistically, DP1 inhibited Th1 activity via the PKA (protein kinase A)/p-Sp1 (phosphorylated specificity protein 1)/neural precursor cell expressed developmentally downregulated 4-like (NEDD4L) pathway–mediated T-box-expressed-in-T-cells (T-bet) ubiquitination. T-bet deletion or forced NEDD4L expression in CD4 + T cells attenuated age-related hypertension in CD4 + T cell–specific DP1-deficient mice. DP1 receptor activation by BW245C prevented age-associated blood pressure elevation and reduced vascular/renal superoxide production in male mice. Conclusions: The prostaglandin D 2 /DP1 axis suppresses age-related Th1 activation and subsequent hypertensive response in male mice through increase of NEDD4L–mediated T-bet degradation by ubiquitination. Therefore, the T cell DP1 receptor may be an attractive therapeutic target for age-related hypertension.

scholarly journals Age-related pacemaker deterioration is due to impaired intracellular and membrane mechanisms: Insights from numerical modeling

2017 ◽  
Vol 149 (10) ◽  
pp. 935-949 ◽  
Author(s):  
Joachim Behar ◽  
Yael Yaniv
Keyword(s):  
Numerical Model ◽  
Firing Rate ◽  
Receptor Activation ◽  
Receptor Stimulation ◽  
Age Related ◽  
Pacemaker Function ◽  
Beating Rate ◽  
Pde Inhibition ◽  
Posttranslation Modification ◽  
Intracellular Mechanisms

Age-related deterioration of pacemaker function has been documented in mammals, including humans. In aged isolated sinoatrial node tissues and cells, reduction in the spontaneous action potential (AP) firing rate was associated with deterioration of intracellular and membrane mechanisms; however, their relative contribution to age-associated deficient pacemaker function is not known. Interestingly, pharmacological interventions that increase posttranslation modification signaling activities can restore the basal and maximal AP firing rate, but the identities of the protein targets responsible for AP firing rate restoration are not known. Here, we developed a numerical model that simulates the function of a single mouse pacemaker cell. In addition to describing membrane and intracellular mechanisms, the model includes descriptions of autonomic receptor activation pathways and posttranslation modification signaling cascades. The numerical model shows that age-related deterioration of pacemaker function is related to impaired intracellular and membrane mechanisms: HCN4, T-type channels, and phospholamban functions, as well as the node connecting these mechanisms, i.e., intracellular Ca2+ and posttranslation modification signaling. To explain the restored maximal beating rate in response to maximal phosphodiesterase (PDE) inhibition, autonomic receptor stimulation, or infused cyclic adenosine monophosphate (cAMP), the model predicts that phospholamban phosphorylation by protein kinase A (PKA) and HCN4 sensitivity to cAMP are altered in advanced age. Moreover, alteration in PKA and cAMP sensitivity can also explain age-reduced sensitivity to PDE inhibition and autonomic receptor stimulation. Finally, the numerical model suggests two pharmacological approaches and one gene manipulation method to restore the basal beating rate of aged pacemaker cells to that of normal adult cells. In conclusion, our numerical model shows that impaired membrane and intracellular mechanisms and the nodes that couple them can lead to deteriorated pacemaker function. By increasing posttranslation modification signaling, the deteriorated basal and maximal age-associated beating rate can be restored to adult levels.

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