scholarly journals Molecular mechanisms of the physiological functions of the aryl hydrocarbon (dioxin) receptor, a multifunctional regulator that senses and responds to environmental stimuli

2010 ◽  
Vol 86 (1) ◽  
pp. 40-53 ◽  
Author(s):  
Yoshiaki FUJII-KURIYAMA ◽  
Kaname KAWAJIRI
Keyword(s):  
Molecular Mechanisms ◽  
Physiological Functions ◽  
Environmental Stimuli ◽  
Aryl Hydrocarbon ◽  
Dioxin Receptor

scholarly journals MECHANISMS IN ENDOCRINOLOGY: Aging and anti-aging: a Combo-Endocrinology overview

2017 ◽  
Vol 176 (6) ◽  
pp. R283-R308 ◽  
Author(s):  
Evanthia Diamanti-Kandarakis ◽  
Maurizio Dattilo ◽  
Djuro Macut ◽  
Leonidas Duntas ◽  
Efstathios S Gonos ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Molecular Mechanisms ◽  
Dynamic Effect ◽  
The Elderly ◽  
Time Dependent ◽  
Endocrine Function ◽  
Scientific Society ◽  
Physiological Functions ◽  
Environmental Stimuli

Aging and its underlying pathophysiological background has always attracted the attention of the scientific society. Defined as the gradual, time-dependent, heterogeneous decline of physiological functions, aging is orchestrated by a plethora of molecular mechanisms, which vividly interact to alter body homeostasis. The ability of an organism to adjust to these alterations, in conjunction with the dynamic effect of various environmental stimuli across lifespan, promotes longevity, frailty or disease. Endocrine function undergoes major changes during aging, as well. Specifically, alterations in hormonal networks and concomitant hormonal deficits/excess, augmented by poor sensitivity of tissues to their action, take place. As hypothalamic–pituitary unit is the central regulator of crucial body functions, these alterations can be translated in significant clinical sequelae that can impair the quality of life and promote frailty and disease. Delineating the hormonal signaling alterations that occur across lifespan and exploring possible remedial interventions could possibly help us improve the quality of life of the elderly and promote longevity.

scholarly journals Exactly the Same but Different: Promiscuity and Diversity in the Molecular Mechanisms of Action of the Aryl Hydrocarbon (Dioxin) Receptor

2011 ◽  
Vol 124 (1) ◽  
pp. 1-22 ◽  
Author(s):  
Michael S. Denison ◽  
Anatoly A. Soshilov ◽  
Guochun He ◽  
Danica E. DeGroot ◽  
Bin Zhao
Keyword(s):  
Molecular Mechanisms ◽  
Mechanisms Of Action ◽  
Aryl Hydrocarbon ◽  
Dioxin Receptor

Role of the ligand in intracellular receptor function: receptor affinity determines activation in vitro of the latent dioxin receptor to a DNA-binding form

1991 ◽  
Vol 11 (1) ◽  
pp. 401-411
Author(s):  
S Cuthill ◽  
A Wilhelmsson ◽  
L Poellinger
Keyword(s):  
Dna Binding ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Rank Order ◽  
Receptor Ligands ◽  
Free System ◽  
Dioxin Receptor

To reconstitute the molecular mechanisms underlying the cellular response to soluble receptor ligands, we have exploited a cell-free system that exhibits signal- (dioxin-)induced activation of the latent cytosolic dioxin receptor to an active DNA-binding species. The DNA-binding properties of the in vitro-activated form were qualitatively indistinguishable from those of in vivo-activated nuclear receptor extracted from dioxin-treated cells. In vitro activation of the receptor by dioxin was dose dependent and was mimicked by other dioxin receptor ligands in a manner that followed the rank order of their relative affinities for the receptor in vitro and their relative potencies to induce target gene transcription in vivo. Thus, in addition to triggering the initial release of inhibition of DNA binding and presumably allowing nuclear translocation, the ligand appears to play a crucial role in the direct control of the level of functional activity of a given ligand-receptor complex.

FC 006PP2A PHOSPHATASE INHIBITION IS ANTI-FIBROTIC THROUGH SER77 PHOSPHORYLATION-MEDIATED ARNT/ARNT HOMODIMER FORMATION

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Gunsmaa Nyamsuren ◽  
Gregor Christof Rapp ◽  
Björn Tampe ◽  
Michael Zeisberg
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Phosphorylation Site ◽  
Receptor Expression ◽  
Proximity Ligation Assay ◽  
Proximity Ligation ◽  
Aryl Hydrocarbon ◽  
Ureter Obstruction

Abstract Background and Aims Aryl hydrocarbon receptor nuclear translocator (ARNT) mediates anti-fibrotic activity in kidney and liver through induction of ALK3-receptor expression and subsequently increased Smad1/5/8 signaling. While expression of ARNT can be pharmacologically induced by sub-immunosuppressive doses of FK506 or by GPI1046, its anti-fibrotic activity is only realized when ARNT-ARNT homodimers form, as opposed to formation of ARNT-AHR or ARNT-HIF1α heterodimers. Mechanisms underlying ARNTs dimerization decision to specifically form ARNT-ARNT homodimers and possible cues to specifically induce ARNT homodimerization have been previously unknown. We here aimed to elucidate the molecular mechanisms underlying control of ARNT dimerization decision and to explore its therapeutic potential. Method We analyzed dimerization of recombinant and native ARNT by immunoprecipitation, MALDI-TOF mass spectrometry, and LS-MS/MS analysis and proximity ligation assay. Phosphorylation sites were mapped through generation of phosphorylation site mutants and through pharmacological inhibition. For in vivo analysis we challenged mice with model of unilateral ureter obstruction and carbon tetrachloride to induce fibrosis in kidney and liver. Results Here we report that inhibition of PP2A phosphatase activity increases intracellular accumulation of ARNT-ARNT homodimers. This effect is dependent on enhanced ARNT-ARNT homodimerization and decreased ARNT proteolytic degradation, but independent of ARNT transcription (which remains unchanged upon PP2A inhibition). We further identify that Ser77 phosphorylation plays a critical role in ARNT homodimerization, as ARNT-ARNT homodimers do not form with Ser77/Asp-mutant ARNT proteins. In light of previous studies which identified anti-fibrotic activity upon increased ARNT expression, we further demonstrate attenuated fibrosis upon monotherapy with the PP2A inhibitor LB100, and additive anti-fibrotic activities upon combination with pharmacological inducers of ARNT expression FK506 or GPI1046 in murine models of kidney and liver fibrosis. Conclusion Our study provides additional evidence for the anti-fibrotic activity of ARNT and reveals Ser77 phosphorylation as a novel pharmacological target to realize the therapeutic potential of increased ARNT transactivation activity.

scholarly journals Environmental Benzopyrene Attenuates Stemness of Placenta-Derived Mesenchymal Stem Cells via Aryl Hydrocarbon Receptor

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
June Seok Heo ◽  
Ja-Yun Lim ◽  
Sangshin Pyo ◽  
Dae Wui Yoon ◽  
Dongsook Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Aryl Hydrocarbon Receptor ◽  
Molecular Mechanisms ◽  
Cell Activity ◽  
Bone Diseases ◽  
Purine Derivative ◽  
Aryl Hydrocarbon ◽  
Polycyclic Aromatic

The toxic effects of particulate matter have been linked to polycyclic aromatic hydrocarbons (PAHs) such as benzopyrene. PAHs are potent inducers of the aryl hydrocarbon receptor (AhR), which is an expressed nuclear receptor that senses environmental stimuli and modulates gene expression. Even though several studies have shown that the benzopyrene (BP) of chemical pollutants significantly impaired stem cell activity, the exact molecular mechanisms were not clearly elucidated. In the present study, we aimed to investigate the effects of BP on placenta-derived mesenchymal stem cells (PD-MSCs) in vitro. We found that the AhR in PD-MSCs was expressed under the treatment of BP, and its activation markedly disrupted osteogenic differentiation through the alteration of stemness activity of PD-MSCs. Moreover, BP treatment significantly reduced the proliferation activity of PD-MSCs and expression of pluripotent markers through the induction of AhR. Treatment with StemRegenin 1 (SR1), a purine derivative that antagonizes the AhR, effectively prevented BP-induced reduction of the proliferation and differentiation activity of PD-MSCs. In this study, we found that BP treatment in PD-MSCs markedly obstructs PD-MSC stemness through AhR signaling. Noteworthy, SR1-mediated MSC application will contribute to new perspectives on MSC-based therapies for air pollution-related bone diseases.

scholarly journals SLC transporters as a novel class of tumour suppressors: identity, function and molecular mechanisms

2016 ◽  
Vol 473 (9) ◽  
pp. 1113-1124 ◽  
Author(s):  
Yangzom D. Bhutia ◽  
Ellappan Babu ◽  
Sabarish Ramachandran ◽  
Shengping Yang ◽  
Muthusamy Thangaraju ◽  
...  
Keyword(s):  
Gene Family ◽  
Molecular Mechanisms ◽  
Physiological Functions ◽  
Identity Function ◽  
Suppressive Function ◽  
Slc Transporters ◽  
Tumour Suppressors ◽  
Tumour Suppressive Function

Four transporters belonging to the SLC gene family (SLC5A8, SLC26A3, SLC39A1 and SLC22A18) have been identified thus far as tumour suppressors; this review summarizes the physiological functions of these transporters and the molecular mechanisms related to their tumour-suppressive function.

A Thylakoid-Located Two-Pore K+ Channel Controls Photosynthetic Light Utilization in Plants

Science ◽  
2013 ◽  
Vol 342 (6154) ◽  
pp. 114-118 ◽  
Author(s):  
Luca Carraretto ◽  
Elide Formentin ◽  
Enrico Teardo ◽  
Vanessa Checchetto ◽  
Martino Tomizioli ◽  
...  
Keyword(s):  
Thylakoid Membrane ◽  
Proton Motive Force ◽  
Motive Force ◽  
K Channel ◽  
Channel Activity ◽  
Membrane Organization ◽  
Physiological Functions ◽  
Environmental Stimuli ◽  
Light Utilization ◽  
Selective Channel

The size of the light-induced proton motive force (pmf) across the thylakoid membrane of chloroplasts is regulated in response to environmental stimuli. Here, we describe a component of the thylakoid membrane, the two-pore potassium (K+) channel TPK3, which modulates the composition of the pmf through ion counterbalancing. Recombinant TPK3 exhibited potassium-selective channel activity sensitive to Ca2+ and H+. In Arabidopsis plants, the channel is found in the thylakoid stromal lamellae. Arabidopsis plants silenced for the TPK3 gene display reduced growth and altered thylakoid membrane organization. This phenotype reflects an impaired capacity to generate a normal pmf, which results in reduced CO2 assimilation and deficient nonphotochemical dissipation of excess absorbed light. Thus, the TPK3 channel manages the pmf necessary to convert photochemical energy into physiological functions.

Sign in / Sign up

Export Citation Format

Share Document