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The Role of Iron in Benign and Malignant Hematopoiesis.
Sinha, S, Pereira-Reis, J, Guerra, A, Rivella, S, Duarte, D
Antioxidants & redox signaling. 2021;(6):415-432
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Abstract
Significance: Iron is an essential element required for sustaining a normal healthy life. However, an excess amount of iron in the bloodstream and tissue generates toxic hydroxyl radicals through Fenton reactions. Henceforth, a balance in iron concentration is extremely important to maintain cellular homeostasis in both normal hematopoiesis and erythropoiesis. Iron deficiency or iron overload can impact hematopoiesis and is associated with many hematological diseases. Recent Advances: The mechanisms of action of key iron regulators such as erythroferrone and the discovery of new drugs, such as ACE-536/luspatercept, are of potential interest to treat hematological disorders, such as β-thalassemia. New therapies targeting inflammation-induced ineffective erythropoiesis are also in progress. Furthermore, emerging evidences support differential interactions between iron and its cellular antioxidant responses of hematopoietic and neighboring stromal cells. Both iron and its systemic regulator, such as hepcidin, play a significant role in regulating erythropoiesis. Critical Issues: Significant pre-clinical studies are on the way and new drugs targeting iron metabolism have been recently approved or are undergoing clinical trials to treat pathological conditions with impaired erythropoiesis such as myelodysplastic syndromes or β-thalassemia. Future Directions: Future studies should explore how iron regulates hematopoiesis in both benign and malignant conditions. Antioxid. Redox Signal. 35, 415-432.
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The role of Elabela in kidney disease.
Zheng, Q, Tian, G, Xu, F, Ci, X, Luan, R, Wu, L, Lu, X
International urology and nephrology. 2021;(9):1851-1857
Abstract
Elabela, also known as Toddler or Apela, is a recently discovered hormonal peptide containing 32 amino acids. Elabela is a ligand of the apelin receptor (APJ). APJ is a G protein-coupled receptor widely expressed throughout body, and together with its cognate ligand, apelin, it plays an important role in various physiological processes including cardiovascular functions, angiogenesis and fluid homeostasis. Elabela also participates in embryonic development and pathophysiological processes in adulthood. Elabela is highly expressed in undifferentiated embryonic stem cells and regulates endoderm differentiation and cardiovascular system development. During differentiation, Elabela is highly expressed in pluripotent stem cells and in adult renal collecting ducts and loops, where it functions to maintain water and sodium homeostasis. Other studies have also shown that Elabela plays a crucial role in the pathogenesis of kidney diseases. This review addresses the role of Elabela in kidney diseases including renal ischemia/reperfusion injury, hypertensive nephropathy, diabetic nephropathy, and cardiorenal syndrome.
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ANGPTL8 in metabolic homeostasis: more friend than foe?
Guo, C, Wang, C, Deng, X, He, J, Yang, L, Yuan, G
Open biology. 2021;(9):210106
Abstract
ANGPTL8 is an important cytokine, which is significantly increased in type 2 diabetes mellitus (T2DM), obesity and metabolic syndrome. Many studies have shown that ANGPTL8 can be used as a bio-marker of these metabolic disorders related diseases, and the baseline ANGPTL8 level has also been found to be positively correlated with retinopathy and all-cause mortality in patients with T2DM. This may be related to the inhibition of lipoprotein lipase activity and the reduction of circulating triglyceride (TG) clearance by ANGPTL8. Consistently, inhibition of ANGPTL8 seems to prevent or improve atherosclerosis. However, it is puzzling that ANGPTL8 seems to have a directing function for TG uptake in peripheral tissues; that is, ANGPTL8 specifically enhances the reserve and buffering function of white adipose tissue, which may alleviate the ectopic lipid accumulation to a certain extent. Furthermore, ANGPTL8 can improve insulin sensitivity and inhibit hepatic glucose production. These contradictory results lead to different opinions on the role of ANGPTL8 in metabolic disorders. In this paper, the correlation between ANGPTL8 and metabolic diseases, the regulation of ANGPTL8 and the physiological role of ANGPTL8 in the process of glucose and lipid metabolism were summarized, and the physiological/pathological significance of ANGPTL8 in the process of metabolic disorder was discussed.
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Regulation of plant peptide hormones and growth factors by post-translational modification.
Stührwohldt, N, Schaller, A
Plant biology (Stuttgart, Germany). 2019;:49-63
Abstract
The number, diversity and significance of peptides as regulators of cellular differentiation, growth, development and defence of plants has long been underestimated. Peptides have now emerged as an important class of signals for cell-to-cell communication over short distances, and also for long-range signalling. We refer to these signalling molecules as peptide growth factors and peptide hormones, respectively. As compared to remarkable progress with respect to the mechanisms of peptide perception and signal transduction, the biogenesis of signalling peptides is still in its infancy. This review focuses on the biogenesis and activity of small post-translationally modified peptides. These peptides are derived from inactive pre-pro-peptides of approximately 70-120 amino acids. Multiple post-translational modifications (PTMs) may be required for peptide maturation and activation, including proteolytic processing, tyrosine sulfation, proline hydroxylation and hydroxyproline glycosylation. While many of the enzymes responsible for these modifications have been identified, their impact on peptide activity and signalling is not fully understood. These PTMs may or may not be required for bioactivity, they may inactivate the peptide or modify its signalling specificity, they may affect peptide stability or targeting, or its binding affinity with the receptor. In the present review, we will first introduce the peptides that undergo PTMs and for which these PTMs were shown to be functionally relevant. We will then discuss the different types of PTMs and the impact they have on peptide activity and plant growth and development. We conclude with an outlook on the open questions that need to be addressed in future research.
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5.
Sulfated plant peptide hormones.
Kaufmann, C, Sauter, M
Journal of experimental botany. 2019;(16):4267-4277
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Abstract
Sulfated peptides are plant hormones that are active at nanomolar concentrations. The sulfation at one or more tyrosine residues is catalysed by tyrosylprotein sulfotransferase (TPST), which is encoded by a single-copy gene. The sulfate group is provided by the co-substrate 3´-phosphoadenosine 5´-phosphosulfate (PAPS), which links synthesis of sulfated signaling peptides to sulfur metabolism. The precursor proteins share a conserved DY-motif that is implicated in specifying tyrosine sulfation. Several sulfated peptides undergo additional modification such as hydroxylation of proline and glycosylation of hydroxyproline. The modifications render the secreted signaling molecules active and stable. Several sulfated signaling peptides have been shown to be perceived by leucine-rich repeat receptor-like kinases (LRR-RLKs) but have signaling pathways that, for the most part, are yet to be elucidated. Sulfated peptide hormones regulate growth and a wide variety of developmental processes, and intricately modulate immunity to pathogens. While basic research on sulfated peptides has made steady progress, their potential in agricultural and pharmaceutical applications has yet to be explored.
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The Impact of Obstructive Sleep Apnea and Positive Airway Pressure Therapy on Metabolic Peptides Regulating Appetite, Food Intake, Energy Homeostasis, and Systemic Inflammation: A Literature Review.
Mashaqi, S, Badr, MS
Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2019;(7):1037-1050
Abstract
INTRODUCTION Sleep-related breathing disorders are very common and highly associated with many comorbid diseases. They have many metabolic consequences that impact appetite, energy expenditure, and systemic inflammation. These consequences are mediated through peptides (eg, ghrelin, leptin, adiponectin, resistin, apelin, obestatin, and neuropeptide Y). METHODS We searched the literature (PubMed) for sleep-disordered breathing (SDB) and metabolic peptides and included 15, 22, 14, 4 and 2 articles for ghrelin, leptin, adiponectin, resistin, and apelin respectively. RESULTS Our review of the published literature suggests that leptin levels seem to correlate with body mass index and adiposity rather than obstructive sleep apnea. Conversely, levels of adiponectin and ghrelin are influenced by obstructive sleep apnea alone. Finally, resistin and apelin seem to be not correlated with obstructive sleep apnea. Regarding positive airway pressure (PAP) impact, it seems that PAP therapy affected the levels of these peptides (mainly ghrelin). CONCLUSIONS There is significant controversy in the literature regarding the impact of SDB and PAP therapy on these metabolic peptides. This could be due to the lack of randomized clinical trials and the variability of the methodology used in these studies. Further research is needed to assess the impact of SDB and PAP therapy on the levels of these peptides and whether this impact is also related to body mass index and body fat composition.
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CEP peptide hormones: key players in orchestrating nitrogen-demand signalling, root nodulation, and lateral root development.
Taleski, M, Imin, N, Djordjevic, MA
Journal of experimental botany. 2018;(8):1829-1836
Abstract
Secreted peptide hormones play pivotal roles in plant growth and development. So far, CEPs (C-TERMINALLY ENCODED PEPTIDEs) have been shown to act through CEP receptors (CEPRs) to control nitrogen (N)-demand signalling, nodulation, and lateral root development. Secreted CEP peptides can enter the xylem stream to act as long-distance signals, but evidence also exists for CEPs acting in local circuits. Recently, CEP peptide species varying in sequence, length, and post-translational modifications have been identified. A more comprehensive understanding of CEP biology requires insight into the in planta function of CEP genes, CEP peptide biogenesis, the components of CEP signalling cascades and, finally, how CEP peptide length, amino-acid composition, and post-translational modifications affect biological activity. In this review, we highlight recent studies that have advanced our understanding in these key areas and discuss some future directions.
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Peptide Hormones as Tumor Markers in Clinical Practice.
Sun, Q, Zhao, Z
The Enzymes. 2017;:65-79
Abstract
Peptide hormones represent a major class of hormones that are made from amino acids by specialized endocrine glands. The maturation of bioactive hormones take place in the rough endoplasmic reticulum and Golgi apparatus, where preprohormones are proteolytically cleaved into prohormones, and subsequently into mature peptide hormones. Once the bioactive hormones are released into the circulation, they interact with receptors located on the plasma membrane of target cells, and initiate intracellular signaling pathways to regulate physiological processes including energy metabolism, growth, stress, and reproduction. However, excessive amount of circulating peptide hormones often associates with the presence of tumors. Section 2 discusses 10 peptide hormones as tumor markers and their clinical application in aiding the diagnosis of tumors as well as monitoring the disease process.
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ANGPTL8 (betatrophin) role in diabetes and metabolic diseases.
Abu-Farha, M, Abubaker, J, Tuomilehto, J
Diabetes/metabolism research and reviews. 2017;(8)
Abstract
Diabetes is a major disease worldwide that is reaching epidemic levels. Its increased prevalence as well as its association with a high number of complications such as cardiovascular diseases, nephropathy, and retinopathy makes it an important disease for investigation. ANGPTL8 is a recently identified hormone that has been associated with two functionally important processes in the development of type 2 diabetes, insulin resistance as well as lipid metabolism. Initial work has shown that ANGPTL8 was expressed in liver, white adipose, and brown adipose tissues. ANGPTL8 regulates the activity of lipoprotein lipase, which is a key enzyme in lipoprotein lipolysis pathway through its direct interaction with ANGPTL3. It has been also reported that it regulates the replication of β-cells in response to insulin resistance. As a result, many recent studies have focused on the association of ANGPTL8 with diabetes and obesity as well as its association with various metabolic markers in order to better understand its physiological role in glucose homeostasis and lipid metabolism. In this review, we will highlight some of the key clinical findings, mainly from human studies, that investigated the role of ANGPTL8 in metabolic diseases such as diabetes, obesity, and the metabolic syndrome.
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The effect of zinc supplementation on body composition and hormone levels related to adiposity among children: a systematic review.
Gunanti, IR, Al-Mamun, A, Schubert, L, Long, KZ
Public health nutrition. 2016;(16):2924-2939
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Abstract
OBJECTIVE To provide a comprehensive synthesis of the effects of Zn supplementation on childhood body composition and adiposity-related hormone levels. DESIGN Five electronic databases were searched for randomized controlled trials of Zn supplementation studies published before 28 February 2015. No statistical pooling of results was carried out due to diversity in study designs. SETTING Community- or hospital-based, from fourteen developing and developed countries. SUBJECTS Children and adolescents aged 0 to 10 years. RESULTS Seven of the fourteen studies reported an overall or subgroup effect of Zn supplementation on at least one parameter of body composition, when determined by anthropometric measurements (increased mid upper-arm circumference, triceps skinfold, subscapular skinfold and mid upper-arm muscle area, and decreased BMI). Three out of the fourteen studies reported increased mean value of total body water estimated by bio-impedance analysis and increased fat-free mass estimated by dual energy X-ray absorptiometry and by total body water. Zn supplementation was associated with increased fat-free mass among stunted children. One study found supplementation decreased leptin and insulin concentrations. CONCLUSIONS Due to the use of anthropometry when determining body composition, a majority of the studies could not accurately address whether alterations in the fat and/or fat-free mass components of the body were responsible for the observed changes in body composition. The effect of Zn supplementation on body composition is not consistent but may modify fat-free mass among children with pre-existing growth failure.