scholarly journals A master of all trades – linking retinoids to different signalling pathways through the multi-purpose receptor STRA6

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Vinesh Dhokia ◽  
Salvador Macip
Keyword(s):  
Vitamin A ◽  
Cell Fate ◽  
Therapeutic Strategies ◽  
Membrane Receptor ◽  
Signalling Pathways ◽  
The Novel ◽  
Entry And Exit ◽  
Cellular Effects ◽  
Cellular Entry ◽  
Key Pathways

AbstractRetinoids are a group of vitamin A-related chemicals that are essential to chordate mammals. They regulate a number of basic processes, including embryogenesis and vision. From ingestion to metabolism and the subsequent cellular effects, retinoid levels are tightly regulated in the organism to prevent toxicity. One component of this network, the membrane receptor STRA6, has been shown to be essential in facilitating the cellular entry and exit of retinol. However, recent data suggests that STRA6 may not function merely as a retinoid transporter but also act as a complex signalling hub in its own right, being able to affect cell fate through the integration of retinoid signalling with other key pathways, such as those involving p53, JAK/STAT, Wnt/β catenin and calcium. This may open new therapeutic strategies in diseases like cancer, where these pathways are often compromised. Here, we look at the growing evidence regarding the novel roles of STRA6 beyond its well characterized classic functions.

Nuclear and membrane receptor-mediated signalling pathways modulate polyamine biosynthesis and interconversion

2007 ◽  
Vol 35 (2) ◽  
pp. 386-390 ◽  
Author(s):  
B. Grzelakowska-Sztabert ◽  
M. Dudkowska ◽  
M. Manteuffel-Cymborowska
Keyword(s):  
Cell Fate ◽  
Cross Talk ◽  
Membrane Receptor ◽  
Signalling Pathways ◽  
Critical Determinant ◽  
Polyamine Biosynthesis ◽  
Adenosylmethionine Decarboxylase ◽  
Cell Growth And Differentiation ◽  
Selective Increase ◽  
Hepatocyte Growth

Polyamines play an important role in cell growth and differentiation, while their overproduction has potentially oncogenic consequences. Polyamine homoeostasis, a critical determinant of cell fate, is precisely tuned at the level of biosynthesis, degradation and transport. The enzymes ODC (ornithine decarboxylase), AdoMetDC (S-adenosylmethionine decarboxylase) and SSAT (spermidine/spermine N1-acetyltransferase) are critical for polyamine pool maintenance. Our experiments were designed to examine the expression of these enzymes in testosterone-induced hypertrophic and antifolate-induced hyperplastic mouse kidney, characterized by activation of AR (androgen receptor) and HGF (hepatocyte growth factor) membrane receptor c-Met respectively. The expression of these key enzymes was up-regulated by antifolate CB 3717 injury-evoked activation of HGF/c-Met signalling. In contrast, activation of the testosterone/AR pathway remarkably induced a selective increase in ODC expression without affecting other enzymes. Studies in catecholamine-depleted kidneys point to a synergistic interaction between the signalling pathways activated via cell membrane catecholamine receptors and AR, as well as c-Met. We found that this cross-talk modulated the expression of ODC and AdoMetDC, enzymes limiting polyamine biosynthesis, but not SSAT. This is in contrast with the antagonistic cross-talk between AR- and c-Met-mediated signalling which negatively regulated the expression of ODC, but affected neither AdoMetDC nor SSAT.

scholarly journals Tumor Suppressor SMAR1 Activates and Stabilizes p53 through Its Arginine-Serine-rich Motif

2005 ◽  
Vol 280 (16) ◽  
pp. 16019-16029 ◽  
Author(s):  
Archana Jalota ◽  
Kamini Singh ◽  
Lakshminarasimhan Pavithra ◽  
Ruchika Kaul-Ghanekar ◽  
Shahid Jameel ◽  
...  
Keyword(s):  
Cell Fate ◽  
The Novel ◽  
Nuclear Retention ◽  
Post Translational Modifications ◽  
Rich Domain ◽  
Dna Damaging Agents ◽  
Proliferation And Apoptosis ◽  
Interfering Rna ◽  
The Guardian

Various stresses and DNA-damaging agents trigger transcriptional activity of p53 by post-translational modifications, making it a global regulatory switch that controls cell proliferation and apoptosis. Earlier we have shown that the novel MAR-associated protein SMAR1 interacts with p53. Here we delineate the minimal domain of SMAR1 (the arginine-serine-rich domain) that is phosphorylated by protein kinase C family proteins and is responsible for p53 interaction, activation, and stabilization within the nucleus. SMAR1-mediated stabilization of p53 is brought about by inhibiting Mdm2-mediated degradation of p53. We also demonstrate that this arginine-serine (RS)-rich domain triggers the various cell cycle modulating proteins that decide cell fate. Furthermore, phenotypic knock-down experiments using small interfering RNA showed that SMAR1 is required for activation and nuclear retention of p53. The level of phosphorylated p53 was significantly increased in the thymus of SMAR1 transgenic mice, showingin vivosignificance of SMAR1 expression. This is the first report that demonstrates the mechanism of action of the MAR-binding protein SMAR1 in modulating the activity of p53, often referred to as the “guardian of the genome.”

scholarly journals Neurosensory Rehabilitation and Olfactory Network Recovery in Covid-19-Related Olfactory Dysfunction

2021 ◽  
Vol 11 (6) ◽  
pp. 686
Author(s):  
Tom Wai-Hin Chung ◽  
Hui Zhang ◽  
Fergus Kai-Chuen Wong ◽  
Siddharth Sridhar ◽  
Kwok-Hung Chan ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Vitamin A ◽  
Olfactory Bulb ◽  
Olfactory Dysfunction ◽  
The Novel ◽  
Volume Loss ◽  
Oral Vitamin ◽  
Pulmonary Manifestation ◽  
Network Recovery ◽  
Extra Pulmonary

Non-conductive olfactory dysfunction (OD) is an important extra-pulmonary manifestation of coronavirus disease 2019 (COVID-19). Olfactory bulb (OB) volume loss and olfactory network functional connectivity (FC) defects were identified in two patients suffering from prolonged COVID-19-related OD. One patient received olfactory treatment (OT) by the combination of oral vitamin A and smell training via the novel electronic portable aromatic rehabilitation (EPAR) diffusers. After four-weeks of OT, clinical recuperation of smell was correlated with interval increase of bilateral OB volumes [right: 22.5 mm3 to 49.5 mm3 (120%), left: 37.5 mm3 to 42 mm3 (12%)] and improvement of mean olfactory FC [0.09 to 0.15 (66.6%)].

scholarly journals Tales from the crypt: intestinal niche signals in tissue renewal, plasticity and cancer

Open Biology ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. 180120 ◽  
Author(s):  
Maureen Spit ◽  
Bon-Kyoung Koo ◽  
Madelon M. Maurice
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Signalling Pathways ◽  
Intestinal Homeostasis ◽  
Cell Dynamics ◽  
Cell Proliferation And Differentiation ◽  
Colorectal Cancer Cells ◽  
Recent Developments ◽  
Mutational Activation ◽  
Stem Cell Populations

Rapidly renewing tissues such as the intestinal epithelium critically depend on the activity of small-sized stem cell populations that continuously generate new progeny to replace lost and damaged cells. The complex and tightly regulated process of intestinal homeostasis is governed by a variety of signalling pathways that balance cell proliferation and differentiation. Accumulating evidence suggests that stem cell control and daughter cell fate determination is largely dictated by the microenvironment. Here, we review recent developments in the understanding of intestinal stem cell dynamics, focusing on the roles, mechanisms and interconnectivity of prime signalling pathways that regulate stem cell behaviour in intestinal homeostasis. Furthermore, we discuss how mutational activation of these signalling pathways endows colorectal cancer cells with niche-independent growth advantages during carcinogenesis.

scholarly journals Different Therapeutic Strategies to Tackle the Infection Associated with COVID-19

2021 ◽  
Author(s):  
Meemansha Sharma ◽  
Thakur Uttam Singh ◽  
Madhu Cholenahalli Lingaraju ◽  
Subhashree Parida
Keyword(s):  
Human Resources ◽  
Therapeutic Targets ◽  
Treatment Strategies ◽  
Therapeutic Agents ◽  
Therapeutic Strategies ◽  
Morbidity And Mortality ◽  
The Novel ◽  
Present Book ◽  
Short Period

Covid-19 is a pandemic and the whole world is facing the loss in terms of morbidity and mortality of the human resources. Therefore, there is an urgent need for various therapeutic agents or drugs to treat the covid-19 patients. Although, vaccination process is under way, it is not possible to provide the vaccination to whole world in a short period. Therefore, it is an essential strategy to work on the various therapeutic aspects of covid-19 treatment. The present book chapter will discuss and review the various aspects of the treatment strategies of the covid-19. Further, we will provide an overview of the virus and host based potential therapeutic targets along with existing therapeutics which are effective against SARS-CoV-2 virus. Also, the novel vaccines are being developed against covid-19 deadly virus will be discussed.

The effect of vitamin A on the regenerating axolotl limb

Development ◽  
1983 ◽  
Vol 77 (1) ◽  
pp. 273-295
Author(s):  
M. Maden
Keyword(s):  
Retinoic Acid ◽  
Cell Division ◽  
Pattern Formation ◽  
Vitamin A ◽  
Cellular Effects ◽  
Tissue Changes ◽  
Time Of Administration

These experiments describe further investigations into the effects of vitamin A on regenerating limbs. The effects of different retinoids, the time of administration, concentration of vitamin A and histological, autoradiographic and histochemical studies are reported. The most obvious result of vitamin A treatment is to cause proximal elements to regeneratefrom distal amputation levels, that is to cause serial reduplication of pattern inthe proximodistal axis. Retinoic acid was the most potent of the analogues tested and longer times of administration or higher concentrations cause a greater amount of serial reduplication. Various tissue changes have been found which include the inhibition of cell division, loss of cartilage metachromasia, changes in the mucous-secreting properties of the epidermis and an increased packing in the blastemal cells. The significance of these cellular effects in relation to the pattern-formation changes is discussed.

Trehalose pathway regulates filamentation response in Saccharomyces cerevisiae

2021 ◽  
Author(s):  
Revathi Iyer ◽  
Paike Jayadeva Bhat
Keyword(s):  
Cell Fate ◽  
The Novel ◽  
Cell Fate Decision ◽  
Carbon And Nitrogen ◽  
Source Depletion ◽  
Fate Decision ◽  
Diploid Cells ◽  
Opposing Effects ◽  
Pseudohyphal Differentiation ◽  
Glucose Condition

Abstract In Saccharomyces cerevisae , the diploid cells undergo either pseudohyphal differentiation or sporulation in response to carbon and nitrogen source depletion. Distinct pathways are known to regulate the processes of filamentation and sporulation in response to nutritional stress. Here, we report the novel finding that the trehalose pathway which is essential for sporulation, is involved in pseudohyphae formation both via GPR1 as well as RAS2 mediated signaling. Our observations indicate that GPR1 is epistatic over TPS1 in signaling for filamentation. Further, we have demonstrated that the pseudohyphal defect of the ras2 mutant is overcome upon disruption of TPS2 . Thus, our results indicate that TPS1 and TPS2 may be involved in cell fate decision between meiosis and filamentation response under nutrient depleting conditions. Further, monitoring pseudohyphae formation under limiting glucose condition unravelled the possibility that TPS1 and TPS2 exert opposing effects to trigger filamentation response.

scholarly journals HPLC-MS/MS Shows That the Cellular Uptake of All-Trans-Retinoic Acid under Hypoxia Is Downregulated by the Novel Active Agent 5-Methoxyleoligin

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2048
Author(s):  
Armin Sebastian Guntner ◽  
Christian Doppler ◽  
Christian Wechselberger ◽  
David Bernhard ◽  
Wolfgang Buchberger
Keyword(s):  
Myocardial Infarction ◽  
Retinoic Acid ◽  
Vitamin A ◽  
Cell Damage ◽  
Umbilical Vein ◽  
Active Agent ◽  
The Novel ◽  
Novel Therapy ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

All-trans-retinoic acid (atRA) is the essential derivative of vitamin A and is of interest due to its various biological key functions. As shown in the recent literature, atRA also plays a role in the failing heart during myocardial infarction, the leading cause of death globally. To date insufficient mechanistic information has been available on related hypoxia-induced cell damage and reperfusion injuries. However, it has been demonstrated that a reduction in cellular atRA uptake abrogates hypoxia-mediated cell and tissue damage, which may offer a new route for intervention. Consequently, in this study, the effect of the novel cardio-protective compound 5-methoxyleoligin (5ML) on cellular atRA uptake was tested in human umbilical-vein endothelial cells (HUVECs). For this purpose, a high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method was developed to assess intra-cellular levels of the active substance and corresponding levels of vitamin A and its derivatives, including potential cis/trans isomers. This work also focused on light-induced isomerization and the stability of biological sample material to ensure sample integrity and avoid biased conclusions. This study provides evidence of the inhibitory effect of 5ML on cellular atRA uptake, a promising step toward a novel therapy for myocardial infarction.

scholarly journals The multi-faceted functioning portrait of LRF/ZBTB7A

2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Caterina Constantinou ◽  
Magda Spella ◽  
Vasiliki Chondrou ◽  
George P. Patrinos ◽  
Adamantia Papachatzopoulou ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Aerobic Glycolysis ◽  
Specific Cell ◽  
Regulation Of Transcription ◽  
Cancer Type ◽  
Cellular Effects ◽  
Physiological Processes ◽  
Signaling Axis

AbstractTranscription factors (TFs) consisting of zinc fingers combined with BTB (for broad-complex, tram-track, and bric-a-brac) domain (ZBTB) are a highly conserved protein family that comprises a multifunctional and heterogeneous group of TFs, mainly modulating cell developmental events and cell fate. LRF/ZBTB7A, in particular, is reported to be implicated in a wide variety of physiological and cancer-related cell events. These physiological processes include regulation of erythrocyte maturation, B/T cell differentiation, adipogenesis, and thymic insulin expression affecting consequently insulin self-tolerance. In cancer, LRF/ZBTB7A has been reported to act either as oncogenic or as oncosuppressive factor by affecting specific cell processes (proliferation, apoptosis, invasion, migration, metastasis, etc) in opposed ways, depending on cancer type and molecular interactions. The molecular mechanisms via which LRF/ZBTB7A is known to exert either physiological or cancer-related cellular effects include chromatin organization and remodeling, regulation of the Notch signaling axis, cellular response to DNA damage stimulus, epigenetic-dependent regulation of transcription, regulation of the expression and activity of NF-κB and p53, and regulation of aerobic glycolysis and oxidative phosphorylation (Warburg effect). It is a pleiotropic TF, and thus, alterations to its expression status become detrimental for cell survival. This review summarizes its implication in different cellular activities and the commonly invoked molecular mechanisms triggered by LRF/ZBTB7A’s orchestrated action.

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