scholarly journals New Insight into Molecular and Hormonal Connection in Andrology

2021 ◽  
Vol 22 (21) ◽  
pp. 11908
Author(s):  
Davide Francomano ◽  
Valerio Sanguigni ◽  
Paolo Capogrosso ◽  
Federico Deho ◽  
Gabriele Antonini
Keyword(s):  
Sexual Function ◽  
Molecular Mechanisms ◽  
Vascular Wall ◽  
Cell Junction ◽  
Testicular Development ◽  
Cellular Functions ◽  
Inflammatory Site ◽  
Male Sexual Function ◽  
Molecular Patterns ◽  
Insight Into

Hormones and cytokines are known to regulate cellular functions in the testes. These biomolecules induce a broad spectrum of effects on various level of spermatogenesis, and among them is the modulation of cell junction restructuring between Sertoli cells and germ cells in the seminiferous epithelium. Cytokines and androgens are closely related, and both correct testicular development and the maintenance of spermatogenesis depend on their function. Cytokines also play a crucial role in the immune testicular system, activating and directing leucocytes across the endothelial barrier to the inflammatory site, as well as in increasing their adhesion to the vascular wall. The purpose of this review is to revise the most recent findings on molecular mechanisms that play a key role in male sexual function, focusing on three specific molecular patterns, namely, cytokines, miRNAs, and endothelial progenitor cells. Numerous reports on the interactions between the immune and endocrine systems can be found in the literature. However, there is not yet a multi-approach review of the literature underlying the role between molecular patterns and testicular and sexual function.

scholarly journals C-terminal tail polyglycylation and polyglutamylation alter microtubule mechanical properties

2019 ◽  
Author(s):  
Kathryn P. Wall ◽  
Harold Hart ◽  
Thomas Lee ◽  
Cynthia Page ◽  
Taviare L. Hawkins ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Molecular Mechanisms ◽  
High Stress ◽  
Resonance Spectroscopy ◽  
Post Translational Modification ◽  
Cellular Functions ◽  
Peptide Backbone ◽  
Post Translational Modifications ◽  
Intrinsic Stiffness ◽  
Insight Into

ABSTRACTMicrotubules are biopolymers that perform diverse cellular functions. The regulation of microtubule behavior occurs in part through post-translational modification of both the α- and β- subunits of tubulin. One class of modifications is the heterogeneous addition of glycine and glutamate residues to the disordered C-terminal tails of tubulin. Due to their prevalence in stable, high stress cellular structures such as cilia, we sought to determine if these modifications alter the intrinsic stiffness of microtubules. Here we describe the purification and characterization of differentially-modified pools of tubulin from Tetrahymena thermophila. We found that glycylation on the α-C-terminal tail is a key determinant of microtubule stiffness, but does not affect the number of protofilaments incorporated into microtubules. We measured the dynamics of the tail peptide backbone using nuclear magnetic resonance spectroscopy. We found that the spin-spin relaxation rate (R2) showed a pronounced decreased as a function of distance from the tubulin surface for the α-tubulin tail, indicating that the α-tubulin tail interacts with the dimer surface. This suggests that the interactions of the α-C-terminal tail with the tubulin body contributes to the stiffness of the assembled microtubule, providing insight into the mechanism by which glycylation and glutamylation can alter microtubule mechanical properties.SIGNIFICANCEMicrotubules are regulated in part by post-translational modifications including the heterogeneous addition of glycine and glutamate residues to the C-terminal tails. By producing and characterizing differentially-modified tubulin, this work provides insight into the molecular mechanisms of how these modifications alter intrinsic microtubule properties such as flexibility. These results have broader implications for mechanisms of how ciliary structures are able to function under high stress.

scholarly journals Reprogramming of Central Carbon Metabolism in Myeloid Cells upon Innate Immune Receptor Stimulation

Immuno ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 1-14
Author(s):  
Laure Perrin-Cocon ◽  
Olivier Diaz ◽  
Anne Aublin-Gex ◽  
Pierre-Olivier Vidalain ◽  
Vincent Lotteau
Keyword(s):  
Carbon Metabolism ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Central Carbon Metabolism ◽  
Innate Immune ◽  
Cellular Functions ◽  
Myeloid Dendritic Cells ◽  
Glycolytic Activity ◽  
Central Carbon ◽  
Molecular Patterns

Immunometabolism is a relatively new field of research that aims at understanding interconnections between the immune system and cellular metabolism. This is now well-documented for innate immune cells of the myeloid lineage such as macrophages and myeloid dendritic cells (DCs) when they engage their differentiation or activation programs. Several studies have shown that stimulation of DCs or macrophages by the binding of pathogen-associated molecular patterns (PAMPs) to pattern recognition receptors (PRRs) leads to increased glycolytic activity and rewiring of central carbon metabolism. These metabolic modulations are essential to support and settle immunological functions by providing energy and immunoregulatory metabolites. As the understanding of molecular mechanisms progressed, significant differences between cell types and species have also been discovered. Pathways leading to the regulation of central carbon metabolism in macrophages and DCs by PRR signaling and consequences on cellular functions are reviewed here.

scholarly journals Molecular mechanisms by which hormones and cytokines regulate cell junction dynamics in the testis

2009 ◽  
Vol 43 (2) ◽  
pp. 43-51 ◽  
Author(s):  
Wing-Yee Lui ◽  
Will M Lee
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Seminiferous Epithelium ◽  
Cell Junctions ◽  
Cell Junction ◽  
Cellular Functions ◽  
Regulatory Effects ◽  
Factor Α

Hormones and cytokines are known to regulate cellular functions in all tissues including testis. These two groups of biomolecules exert a broad spectrum of effects on various aspects of spermatogenesis. Among them, one of the regulatory effects on spermatogenesis is to modulate cell junction restructuring between Sertoli cells and between Sertoli and germ cells in the seminiferous epithelium. The restructuring of cell junctions is crucial to enable the migration of germ cells along the seminiferous epithelium from the basement membrane towards the tubular lumen, and at the same time for their attachment to Sertoli cells for support. This review will summarize the recent findings that focus on the role of hormones (FSH and testosterone) and cytokines (transforming growth factor-βs and tumor necrosis factor-α) on cell junction restructuring in the testis and the molecular mechanisms.

Resolution-Associated Molecular Patterns (RAMPs) as Endogenous Regulators of Glia Functions in Neuroinflammatory Disease

2020 ◽  
Vol 19 (7) ◽  
pp. 483-494
Author(s):  
Tyler J. Wenzel ◽  
Evan Kwong ◽  
Ekta Bajwa ◽  
Andis Klegeris
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Bioactive Lipids ◽  
Prothymosin Α ◽  
Neuroinflammatory Disease ◽  
Cellular Debris ◽  
Αb Crystallin ◽  
Endogenous Regulators ◽  
The Central Nervous System ◽  
Molecular Patterns

: Glial cells, including microglia and astrocytes, facilitate the survival and health of all cells within the Central Nervous System (CNS) by secreting a range of growth factors and contributing to tissue and synaptic remodeling. Microglia and astrocytes can also secrete cytotoxins in response to specific stimuli, such as exogenous Pathogen-Associated Molecular Patterns (PAMPs), or endogenous Damage-Associated Molecular Patterns (DAMPs). Excessive cytotoxic secretions can induce the death of neurons and contribute to the progression of neurodegenerative disorders, such as Alzheimer’s disease (AD). The transition between various activation states of glia, which include beneficial and detrimental modes, is regulated by endogenous molecules that include DAMPs, cytokines, neurotransmitters, and bioactive lipids, as well as a diverse group of mediators sometimes collectively referred to as Resolution-Associated Molecular Patterns (RAMPs). RAMPs are released by damaged or dying CNS cells into the extracellular space where they can induce signals in autocrine and paracrine fashions by interacting with glial cell receptors. While the complete range of their effects on glia has not been described yet, it is believed that their overall function is to inhibit adverse CNS inflammatory responses, facilitate tissue remodeling and cellular debris removal. This article summarizes the available evidence implicating the following RAMPs in CNS physiological processes and neurodegenerative diseases: cardiolipin (CL), prothymosin α (ProTα), binding immunoglobulin protein (BiP), heat shock protein (HSP) 10, HSP 27, and αB-crystallin. Studies on the molecular mechanisms engaged by RAMPs could identify novel glial targets for development of therapeutic agents that effectively slow down neuroinflammatory disorders including AD.

scholarly journals Clinical Candidates Targeting the ATR–CHK1–WEE1 Axis in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 795
Author(s):  
Lukas Gorecki ◽  
Martin Andrs ◽  
Jan Korabecny
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Patient Survival ◽  
Current Status ◽  
Future Perspectives ◽  
Phase Ii Trials ◽  
Anticancer Treatment ◽  
Positive Outlook ◽  
Insight Into

Selective killing of cancer cells while sparing healthy ones is the principle of the perfect cancer treatment and the primary aim of many oncologists, molecular biologists, and medicinal chemists. To achieve this goal, it is crucial to understand the molecular mechanisms that distinguish cancer cells from healthy ones. Accordingly, several clinical candidates that use particular mutations in cell-cycle progressions have been developed to kill cancer cells. As the majority of cancer cells have defects in G1 control, targeting the subsequent intra‑S or G2/M checkpoints has also been extensively pursued. This review focuses on clinical candidates that target the kinases involved in intra‑S and G2/M checkpoints, namely, ATR, CHK1, and WEE1 inhibitors. It provides insight into their current status and future perspectives for anticancer treatment. Overall, even though CHK1 inhibitors are still far from clinical establishment, promising accomplishments with ATR and WEE1 inhibitors in phase II trials present a positive outlook for patient survival.

scholarly journals Selective packaging of mitochondrial proteins into extracellular vesicles prevents the release of mitochondrial DAMPs

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kiran Todkar ◽  
Lilia Chikhi ◽  
Véronique Desjardins ◽  
Firas El-Mortada ◽  
Geneviève Pépin ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Mitochondrial Proteins ◽  
Control Mechanisms ◽  
Mitochondrial Content ◽  
Sorting Nexin ◽  
Inflammatory Conditions ◽  
Selective Targeting ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Insight Into

AbstractMost cells constitutively secrete mitochondrial DNA and proteins in extracellular vesicles (EVs). While EVs are small vesicles that transfer material between cells, Mitochondria-Derived Vesicles (MDVs) carry material specifically between mitochondria and other organelles. Mitochondrial content can enhance inflammation under pro-inflammatory conditions, though its role in the absence of inflammation remains elusive. Here, we demonstrate that cells actively prevent the packaging of pro-inflammatory, oxidized mitochondrial proteins that would act as damage-associated molecular patterns (DAMPs) into EVs. Importantly, we find that the distinction between material to be included into EVs and damaged mitochondrial content to be excluded is dependent on selective targeting to one of two distinct MDV pathways. We show that Optic Atrophy 1 (OPA1) and sorting nexin 9 (Snx9)-dependent MDVs are required to target mitochondrial proteins to EVs, while the Parkinson’s disease-related protein Parkin blocks this process by directing damaged mitochondrial content to lysosomes. Our results provide insight into the interplay between mitochondrial quality control mechanisms and mitochondria-driven immune responses.

scholarly journals Molecular Pathways Involved in the Development of Congenital Erythrocytosis

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1150
Author(s):  
Jana Tomc ◽  
Nataša Debeljak
Keyword(s):  
Signal Transduction ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Oxygen Affinity ◽  
Molecular Pathways ◽  
Disease Development ◽  
Post Translational Modifications ◽  
Hemoglobin Oxygen Affinity ◽  
Insight Into ◽  
Idiopathic Erythrocytosis

Patients with idiopathic erythrocytosis are directed to targeted genetic testing including nine genes involved in oxygen sensing pathway in kidneys, erythropoietin signal transduction in pre-erythrocytes and hemoglobin-oxygen affinity regulation in mature erythrocytes. However, in more than 60% of cases the genetic cause remains undiagnosed, suggesting that other genes and mechanisms must be involved in the disease development. This review aims to explore additional molecular mechanisms in recognized erythrocytosis pathways and propose new pathways associated with this rare hematological disorder. For this purpose, a comprehensive review of the literature was performed and different in silico tools were used. We identified genes involved in several mechanisms and molecular pathways, including mRNA transcriptional regulation, post-translational modifications, membrane transport, regulation of signal transduction, glucose metabolism and iron homeostasis, which have the potential to influence the main erythrocytosis-associated pathways. We provide valuable theoretical information for deeper insight into possible mechanisms of disease development. This information can be also helpful to improve the current diagnostic solutions for patients with idiopathic erythrocytosis.

scholarly journals Pathomechanisms in the Kidneys in Selected Protozoan Parasitic Infections

2021 ◽  
Vol 22 (8) ◽  
pp. 4209
Author(s):  
Karolina Kot ◽  
Natalia Łanocha-Arendarczyk ◽  
Michał Ptak ◽  
Aleksandra Łanocha ◽  
Elżbieta Kalisińska ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Molecular Mechanisms ◽  
Kidney Injury ◽  
Therapeutic Interventions ◽  
Parasitic Infections ◽  
Injury Mechanisms ◽  
Kidney Involvement ◽  
Leishmania Spp ◽  
Apoptosis Process ◽  
Insight Into

Leishmaniasis, malaria, toxoplasmosis, and acanthamoebiasis are protozoan parasitic infections. They remain important contributors to the development of kidney disease, which is associated with increased patients’ morbidity and mortality. Kidney injury mechanisms are not fully understood in protozoan parasitic diseases, bringing major difficulties to specific therapeutic interventions. The aim of this review is to present the biochemical and molecular mechanisms in kidneys infected with Leishmania spp., Plasmodium spp., Toxoplasma gondii, and Acanthamoeba spp. We present available mechanisms of an immune response, oxidative stress, apoptosis process, hypoxia, biomarkers of renal injury in the serum or urine, and the histopathological changes of kidneys infected with the selected parasites. Pathomechanisms of Leishmania spp. and Plasmodium spp. infections have been deeply investigated, while Toxoplasma gondii and Acanthamoeba spp. infections in the kidneys are not well known yet. Deeper knowledge of kidney involvement in leishmaniasis and malaria by presenting their mechanisms provides insight into how to create novel and effective treatments. Additionally, the presented work shows gaps in the pathophysiology of renal toxoplasmosis and acanthamoebiasis, which need further research.

scholarly journals The apple C2H2-type zinc finger transcription factor MdZAT10 positively regulates JA-induced leaf senescence by interacting with MdBT2

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Kuo Yang ◽  
Jian-Ping An ◽  
Chong-Yang Li ◽  
Xue-Na Shen ◽  
Ya-Jing Liu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Transcription Factor ◽  
Liquid Chromatography ◽  
Zinc Finger ◽  
Leaf Senescence ◽  
Transcriptional Activity ◽  
Molecular Mechanisms ◽  
Liquid Chromatography Mass Spectrometry ◽  
Zinc Finger Transcription Factor ◽  
Insight Into

AbstractJasmonic acid (JA) plays an important role in regulating leaf senescence. However, the molecular mechanisms of leaf senescence in apple (Malus domestica) remain elusive. In this study, we found that MdZAT10, a C2H2-type zinc finger transcription factor (TF) in apple, markedly accelerates leaf senescence and increases the expression of senescence-related genes. To explore how MdZAT10 promotes leaf senescence, we carried out liquid chromatography/mass spectrometry screening. We found that MdABI5 physically interacts with MdZAT10. MdABI5, an important positive regulator of leaf senescence, significantly accelerated leaf senescence in apple. MdZAT10 was found to enhance the transcriptional activity of MdABI5 for MdNYC1 and MdNYE1, thus accelerating leaf senescence. In addition, we found that MdZAT10 expression was induced by methyl jasmonate (MeJA), which accelerated JA-induced leaf senescence. We also found that the JA-responsive protein MdBT2 directly interacts with MdZAT10 and reduces its protein stability through ubiquitination and degradation, thereby delaying MdZAT10-mediated leaf senescence. Taken together, our results provide new insight into the mechanisms by which MdZAT10 positively regulates JA-induced leaf senescence in apple.

Sign in / Sign up

Export Citation Format

Share Document