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Current Opinion in Plant Biology Oct 2023Peptide hormones influence diverse aspects of plant development through highly coordinated cell-cell signaling pathways. Many peptide hormone families play key roles in... (Review)
Review
Peptide hormones influence diverse aspects of plant development through highly coordinated cell-cell signaling pathways. Many peptide hormone families play key roles in stem cell maintenance across land plants. In this review, we focus on recent work in two conserved peptide hormone families, CLAVATA3/EMBRYO-SURROUNDING REGION (CLEs) and ROOT MERISTEM GROWTH FACTOR (RGFs), and their roles in regulating plant stem cells. We discuss recent work establishing downstream crosstalk between peptide hormones and other conserved signaling mechanisms in meristem maintenance as well as highlight advances in peptide hormone gene identification that provide important context for CLE/RGF family evolution across diverse plant lineages. CLE and RGF gene families have greatly expanded in angiosperms, contributing to the complex genetic regulation of stem cell homeostasis observed in model systems over the last 30 years. Peptide hormone duplications have resulted in genetic compensation mechanisms that ensure robust development through the function of paralogous genes. Broad conservation of genetic compensation across angiosperms highlights the importance of these mechanisms in developmental signaling and understanding their regulation could inform broader understanding of morphological diversity and evolutionary innovation.
Topics: Peptide Hormones; Signal Transduction; Stem Cells; Plant Cells; Plant Growth Regulators; Magnoliopsida; Plant Stems
PubMed: 37672866
DOI: 10.1016/j.pbi.2023.102442 -
Endocrine Reviews Jul 2020DNA damage response (DDR) and DNA repair pathways determine neoplastic cell transformation and therapeutic responses, as well as the aging process. Altered DDR... (Review)
Review
DNA damage response (DDR) and DNA repair pathways determine neoplastic cell transformation and therapeutic responses, as well as the aging process. Altered DDR functioning results in accumulation of unrepaired DNA damage, increased frequency of tumorigenic mutations, and premature aging. Recent evidence suggests that polypeptide hormones play a role in modulating DDR and DNA damage repair, while DNA damage accumulation may also affect hormonal status. We review the available reports elucidating involvement of insulin-like growth factor 1 (IGF1), growth hormone (GH), α-melanocyte stimulating hormone (αMSH), and gonadotropin-releasing hormone (GnRH)/gonadotropins in DDR and DNA repair as well as the current understanding of pathways enabling these actions. We discuss effects of DNA damage pathway mutations, including Fanconi anemia, on endocrine function and consider mechanisms underlying these phenotypes. (Endocrine Reviews 41: 1 - 19, 2020).
Topics: Animals; DNA Damage; DNA Repair; Gonadotropin-Releasing Hormone; Gonadotropins; Growth Hormone; Humans; Insulin-Like Growth Factor I; Peptide Hormones; alpha-MSH
PubMed: 32270196
DOI: 10.1210/endrev/bnaa009 -
Molecular Metabolism Apr 2021Non-alcoholic steatohepatitis (NASH) is a spectrum of histological liver pathologies ranging from hepatocyte fat accumulation, hepatocellular ballooning, lobular... (Review)
Review
BACKGROUND
Non-alcoholic steatohepatitis (NASH) is a spectrum of histological liver pathologies ranging from hepatocyte fat accumulation, hepatocellular ballooning, lobular inflammation, and pericellular fibrosis. Based on early investigations, it was discovered that visceral fat accumulation, hepatic insulin resistance, and atherogenic dyslipidemia are pathological triggers for NASH progression. As these pathogenic features are common with obesity, type 2 diabetes (T2D), and atherosclerosis, therapies that target dysregulated core metabolic pathways may hold promise for treating NASH, particularly as first-line treatments.
SCOPE OF REVIEW
In this review, the latest clinical data on nuclear hormone- and peptide hormone-based drug candidates for NASH are reviewed and contextualized, culminating with a discovery research perspective on emerging combinatorial therapeutic approaches that merge nuclear and peptide strategies.
MAJOR CONCLUSION
Several drug candidates targeting the metabolic complications of NASH have shown promise in early clinical trials, albeit with unique benefits and challenges, but questions remain regarding their translation to larger and longer clinical trials, as well as their utility in a more diseased patient population. Promising polypharmacological approaches can potentially overcome some of these perceived challenges, as has been suggested in preclinical models, but deeper characterizations are required to fully evaluate these opportunities.
Topics: Animals; Diabetes Mellitus, Type 2; Dyslipidemias; Fibroblast Growth Factors; Humans; Inflammation; Insulin Resistance; Liver; Nerve Tissue Proteins; Non-alcoholic Fatty Liver Disease; Obesity; Peptide Hormones; Receptors, Cytoplasmic and Nuclear; Receptors, Thyroid Hormone
PubMed: 33359400
DOI: 10.1016/j.molmet.2020.101153 -
Science (New York, N.Y.) Jan 2014Plant cells are immobile; thus, plant growth and development depend on cell expansion rather than cell migration. The molecular mechanism by which the plasma membrane...
Plant cells are immobile; thus, plant growth and development depend on cell expansion rather than cell migration. The molecular mechanism by which the plasma membrane initiates changes in the cell expansion rate remains elusive. We found that a secreted peptide, RALF (rapid alkalinization factor), suppresses cell elongation of the primary root by activating the cell surface receptor FERONIA in Arabidopsis thaliana. A direct peptide-receptor interaction is supported by specific binding of RALF to FERONIA and reduced binding and insensitivity to RALF-induced growth inhibition in feronia mutants. Phosphoproteome measurements demonstrate that the RALF-FERONIA interaction causes phosphorylation of plasma membrane H(+)-adenosine triphosphatase 2 at Ser(899), mediating the inhibition of proton transport. The results reveal a molecular mechanism for RALF-induced extracellular alkalinization and a signaling pathway that regulates cell expansion.
Topics: Arabidopsis; Arabidopsis Proteins; Cell Enlargement; Cell Membrane; Molecular Sequence Data; Peptide Hormones; Phosphorylation; Phosphotransferases; Plant Cells; Plant Roots; Protein Binding; Proteome; Proton-Translocating ATPases; Serine
PubMed: 24458638
DOI: 10.1126/science.1244454 -
Molecules (Basel, Switzerland) Sep 2020Work from our laboratories over the last 35 years that has focused on Ste2p, a G protein-coupled receptor (GPCR), and its tridecapeptide ligand α-factor is reviewed.... (Review)
Review
Work from our laboratories over the last 35 years that has focused on Ste2p, a G protein-coupled receptor (GPCR), and its tridecapeptide ligand α-factor is reviewed. Our work utilized the yeast as a model system for understanding peptide-GPCR interactions. It explored the structure and function of synthetic α-factor analogs and biosynthetic receptor domains, as well as designed mutations of Ste2p. The results and conclusions are described using the nuclear magnetic resonance interrogation of synthetic Ste2p transmembrane domains (TMs), the fluorescence interrogation of agonist and antagonist binding, the biochemical crosslinking of peptide analogs to Ste2p, and the phenotypes of receptor mutants. We identified the ligand-binding domain in Ste2p, the functional assemblies of TMs, unexpected and interesting ligand analogs; gained insights into the bound α-factor structure; and unraveled the function and structures of various Ste2p domains, including the N-terminus, TMs, loops connecting the TMs, and the C-terminus. Our studies showed interactions between specific residues of Ste2p in an active state, but not resting state, and the effect of ligand activation on the dimerization of Ste2p. We show that, using a battery of different biochemical and genetic approaches, deep insight can be gained into the structure and conformational dynamics of GPCR-peptide interactions in the absence of a crystal structure.
Topics: Allosteric Regulation; Binding Sites; Ligands; Microscopy, Fluorescence; Peptide Hormones; Protein Binding; Protein Domains; Receptors, G-Protein-Coupled; Saccharomyces cerevisiae
PubMed: 32961885
DOI: 10.3390/molecules25184272 -
Scientific Reports Jan 2020Hormones within very low levels regulate and control the activity of specific cells and organs of the human body. Hormone imbalance can cause many diseases. Therefore,...
Hormones within very low levels regulate and control the activity of specific cells and organs of the human body. Hormone imbalance can cause many diseases. Therefore, hormone detection tools have been developed, particularly over the last decade. Peptide hormones have a short half-life, so it is important to detect them within a short time. In this study, we report two types of peptide hormone sensors using human hormone receptor-carrying nanovesicles and graphene field-effect transistors (FETs). Parathyroid hormone (PTH) and glucagon (GCG) are peptide hormones present in human blood that act as ligands to G protein-coupled receptors (GPCRs). In this paper, the parathyroid hormone receptor (PTHR) and the glucagon receptor (GCGR) were expressed in human embryonic kidney-293 (HEK-293) cells, and were constructed as nanovesicles carrying the respective receptors. They were then immobilized onto graphene-based FETs. The two hormone sensors developed were able to detect each target hormone with high sensitivity (ca. 100 fM of PTH and 1 pM of GCG). Also, the sensors accurately recognized target hormones among different types of peptide hormones. In the development of hormone detection tools, this approach, using human hormone receptor-carrying nanovesicles and graphene FETs, offers the possibility of detecting very low concentrations of hormones in real-time.
Topics: Biosensing Techniques; Graphite; HEK293 Cells; Humans; Nanoparticles; Peptide Hormones; Receptors, Peptide; Transistors, Electronic
PubMed: 31942024
DOI: 10.1038/s41598-019-57339-1 -
Nutrients Dec 2022The seminal discoveries that parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) are major endocrine regulators of vitamin D metabolism led to a... (Review)
Review
The seminal discoveries that parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) are major endocrine regulators of vitamin D metabolism led to a significant improvement in our understanding of the pivotal roles of peptide hormones and small proteohormones in the crosstalk between different organs, regulating vitamin D metabolism. The interaction of vitamin D, FGF23 and PTH in the kidney is essential for maintaining mineral homeostasis. The proteohormone FGF23 is mainly secreted from osteoblasts and osteoclasts in the bone. FGF23 acts on proximal renal tubules to decrease production of the active form of vitamin D (1,25(OH)D) by downregulating transcription of 1α-hydroxylase (), and by activating transcription of the key enzyme responsible for vitamin D degradation, 24-hydroxylase (). Conversely, the peptide hormone PTH stimulates 1,25(OH)D renal production by upregulating the expression of 1α-hydroxylase and downregulating that of 24-hydroxylase. The circulating concentration of 1,25(OH)D is a positive regulator of FGF23 secretion in the bone, and a negative regulator of PTH secretion from the parathyroid gland, forming feedback loops between kidney and bone, and between kidney and parathyroid gland, respectively. In recent years, it has become clear that vitamin D signaling has important functions beyond mineral metabolism. Observation of seasonal variations in blood pressure and the subsequent identification of vitamin D receptor (VDR) and 1α-hydroxylase in non-renal tissues such as cardiomyocytes, endothelial and smooth muscle cells, suggested that vitamin D may play a role in maintaining cardiovascular health. Indeed, observational studies in humans have found an association between vitamin D deficiency and hypertension, left ventricular hypertrophy and heart failure, and experimental studies provided strong evidence for a role of vitamin D signaling in the regulation of cardiovascular function. One of the proposed mechanisms of action of vitamin D is that it functions as a negative regulator of the renin-angiotensin-aldosterone system (RAAS). This finding established a novel link between vitamin D and RAAS that was unexplored until then. During recent years, major progress has been made towards a more complete understanding of the mechanisms by which FGF23, PTH, and RAAS regulate vitamin D metabolism, especially at the genomic level. However, there are still major gaps in our knowledge that need to be filled by future research. The purpose of this review is to highlight our current understanding of the molecular mechanisms underlying the interaction between vitamin D, FGF23, PTH, and RAAS, and to discuss the role of these mechanisms in physiology and pathophysiology.
Topics: Humans; Fibroblast Growth Factors; Parathyroid Hormone; Peptide Hormones; Renin-Angiotensin System; Vitamin D; Vitamin D3 24-Hydroxylase; Vitamins
PubMed: 36501215
DOI: 10.3390/nu14235186 -
Endocrine Oct 2013The recently discovered nesfatin-1 is regulated by hunger and satiety. The precursor protein NUCB2 is proteolytically cleaved into three resulting fragments: nesfatin-1,... (Review)
Review
The recently discovered nesfatin-1 is regulated by hunger and satiety. The precursor protein NUCB2 is proteolytically cleaved into three resulting fragments: nesfatin-1, nesfatin-2, and nesfatin-3. The middle segment of nesfatin-1 (M30) is responsible for limiting food intake, while the exact physiological role of nesfatin-2 and nesfatin-3 are not currently known yet. This hormone plays role/roles on diabetic hyperphagia, epilepsy, mood, stress, sleeping, anxiety, hyperpolarization, depolarization, and reproductive functions. This review will address nesfatin, focusing on its discovery and designation, biochemical structure, scientific evidence of its anorexigenic character, the results of the human and animal studies until the present day, its main biochemical and physiological effects, and its possible clinical applications.
Topics: Animals; Blood Pressure; Body Temperature; Calcium-Binding Proteins; DNA-Binding Proteins; Eating; Genetic Association Studies; Humans; Nerve Tissue Proteins; Neurons; Nucleobindins; Peptide Hormones; Reproduction; Stress, Psychological
PubMed: 23526235
DOI: 10.1007/s12020-013-9923-0 -
Peptides Sep 2020The peptide hormone adrenomedullin (ADM) consists of 52 amino acids and plays a pivotal role in the regulation of many physiological processes, particularly those of the... (Review)
Review
The peptide hormone adrenomedullin (ADM) consists of 52 amino acids and plays a pivotal role in the regulation of many physiological processes, particularly those of the cardiovascular and lymphatic system. Like calcitonin (CT), calcitonin gene-related peptide (CGRP), intermedin (IMD) and amylin (AMY), it belongs to the CT/CGRP family of peptide hormones, which despite their low little sequence identity share certain characteristic structural features as well as a complex multicomponent receptor system. ADM, IMD and CGRP exert their biological effects by activation of the calcitonin receptor-like receptor (CLR) as a complex with one of three receptor activity-modifying proteins (RAMP), which alter the ligand affinity. Selectivity within the receptor system is largely mediated by the amidated C-terminus of the peptide hormones, which bind to the extracellular domains of the receptors. This enables their N-terminus consisting of a disulfide-bonded ring structure and a helical segment to bind within the transmembrane region and to induce an active receptor confirmation. ADM is expressed in a variety of tissues in the human body and is fundamentally involved in multitude biological processes. Thus, it is of interest as a diagnostic marker and a promising candidate for therapeutic interventions. In order to fully exploit the potential of ADM, it is necessary to improve its pharmacological profile by increasing the metabolic stability and, ideally, creating receptor subtype-selective analogs. While several successful attempts to prolong the half-life of ADM were recently reported, improving or even retaining receptor selectivity remains challenging.
Topics: Adrenomedullin; Animals; Binding Sites; Calcitonin; Calcitonin Gene-Related Peptide; Calcitonin Receptor-Like Protein; Cardiovascular Diseases; Central Nervous System; Gene Expression Regulation; Humans; Islet Amyloid Polypeptide; Lymphatic System; Models, Molecular; Neoplasms; Peptide Hormones; Protein Binding; Signal Transduction
PubMed: 32569606
DOI: 10.1016/j.peptides.2020.170347 -
Physiological Reviews Oct 2009It is now apparent that regulation of blood vessel growth contributes to the classical actions of hormones on development, growth, and reproduction. Endothelial cells... (Review)
Review
It is now apparent that regulation of blood vessel growth contributes to the classical actions of hormones on development, growth, and reproduction. Endothelial cells are ideally positioned to respond to hormones, which act in concert with locally produced chemical mediators to regulate their growth, motility, function, and survival. Hormones affect angiogenesis either directly through actions on endothelial cells or indirectly by regulating proangiogenic factors like vascular endothelial growth factor. Importantly, the local microenvironment of endothelial cells can determine the outcome of hormone action on angiogenesis. Members of the growth hormone/prolactin/placental lactogen, the renin-angiotensin, and the kallikrein-kinin systems that exert stimulatory effects on angiogenesis can acquire antiangiogenic properties after undergoing proteolytic cleavage. In view of the opposing effects of hormonal fragments and precursor molecules, the regulation of the proteases responsible for specific protein cleavage represents an efficient mechanism for balancing angiogenesis. This review presents an overview of the actions on angiogenesis of the above-mentioned peptide hormonal families and addresses how specific proteolysis alters the final outcome of these actions in the context of health and disease.
Topics: Animals; Female; Humans; Neovascularization, Pathologic; Neovascularization, Physiologic; Peptide Hormones; Peptide Hydrolases; Pregnancy; Reproduction
PubMed: 19789380
DOI: 10.1152/physrev.00024.2009