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https://www.readbyqxmd.com/read/28817612/expression-and-functional-implications-of-the-renal-apelinergic-system-in-rodents
#1
Anne-Marie O'Carroll, Sabrine Salih, Philip R Griffiths, Aarifah Bijabhai, Mark A Knepper, Stephen J Lolait
Apelin binds to the G protein-coupled apelin receptor (APJ; gene name aplnr) to modulate diverse physiological systems including cardiovascular function, and hydromineral and metabolic balance. Recently a second endogenous ligand for APJ, named apela, has been discovered. We confirm that apela activates signal transduction pathways (ERK activation) in cells expressing the cloned rat APJ. Previous studies suggest that exogenous apela is diuretic, attributable wholly or in part to an action on renal APJ. Thus far the cellular distribution of apela in the kidney has not been reported...
2017: PloS One
https://www.readbyqxmd.com/read/28811860/the-apelin-receptor-apj-in-hematopoietic-stem-cells-progenitor-cells-in-the-early-stage-of-non-alcoholic-steatohepatitis
#2
Wataru Ando, Hiroaki Yokomori, Katsuya Otori, Masaya Oda
BACKGROUND: Non-alcoholic steatohepatitis (NASH) is characterized by hepatic steatosis and inflammation with or without fibrosis. The apelin receptor (APJ) is related to angiotensin-like-receptor 1 (AGTRL1). The present study aimed to evaluate APJ as an indicator of the pathophysiology of early-stage NASH. METHODS: APJ expression was evaluated in six tissue samples with histologically proven early-stage NASH using immunohistochemistry (IHC) and immunoelectron microscopy (IEM)...
September 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28796300/apelin-apj-system-a-novel-potential-therapy-target-for-kidney-disease
#3
REVIEW
Zhen Huang, Lele Wu, Linxi Chen
Apelin is an endogenous ligand of seven-transmembrane G protein-coupled receptor APJ. Apelin and APJ are distributed in various tissues, including the heart, lung, kidney, and even in tumor tissues. Studies show that apelin mRNA is highly expressed in the inner stripe of kidney outer medulla, which plays an important role in process of water and sodium balance. Additionally, more studies also indicate that apelin/APJ system exerts a broad range of activities in kidney. Therefore, we review the role of apelin/APJ system in kidney diseases such as renal fibrosis, renal ischemia/reperfusion injury, diabetic nephropathy, polycystic kidney disease and hemodialysis...
August 10, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28783722/identification-of-essential-genes-for-cancer-immunotherapy
#4
Shashank J Patel, Neville E Sanjana, Rigel J Kishton, Arash Eidizadeh, Suman K Vodnala, Maggie Cam, Jared J Gartner, Li Jia, Seth M Steinberg, Tori N Yamamoto, Anand S Merchant, Gautam U Mehta, Anna Chichura, Ophir Shalem, Eric Tran, Robert Eil, Madhusudhanan Sukumar, Eva Perez Guijarro, Chi-Ping Day, Paul Robbins, Steve Feldman, Glenn Merlino, Feng Zhang, Nicholas P Restifo
Somatic gene mutations can alter the vulnerability of cancer cells to T-cell-based immunotherapies. Here we perturbed genes in human melanoma cells to mimic loss-of-function mutations involved in resistance to these therapies, by using a genome-scale CRISPR-Cas9 library that consisted of around 123,000 single-guide RNAs, and profiled genes whose loss in tumour cells impaired the effector function of CD8(+) T cells. The genes that were most enriched in the screen have key roles in antigen presentation and interferon-γ signalling, and correlate with cytolytic activity in patient tumours from The Cancer Genome Atlas...
August 7, 2017: Nature
https://www.readbyqxmd.com/read/28782414/protective-effect-of-neuropeptide-apelin-13-on-6-hydroxydopamine-induced-neurotoxicity-in-sh-sy5y-dopaminergic-cells-involvement-of-its-antioxidant-and-antiapoptotic-properties
#5
Elham Pooresmaeili-Babaki, Saeed Esmaeili-Mahani, Mehdi Abbasnejad, Hadi Ravan
Parkinson's disease (PD) is a severe neurodegenerative disorder characterized by the loss of brain dopaminergic neurons. Beside pharmacologic and symptomatic treatment of PD the neuroprotective therapy has recently attracted more attention. Apelin, a novel neuropeptide, and its receptors have numerous reported roles in regulating brain functions. In addition, this peptide has potent neuroprotective effects in some neurodegenerative situations. Here, the effects of apelin-13 were investigated in a cell model of PD...
August 7, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/28777197/elabela-improves-cardio-renal-outcome-in-fatal-experimental-septic-shock
#6
David Coquerel, Frédéric Chagnon, Xavier Sainsily, Lauralyne Dumont, Alexandre Murza, Jérôme Côté, Robert Dumaine, Philippe Sarret, Éric Marsault, Dany Salvail, Mannix Auger-Messier, Olivier Lesur
OBJECTIVES: Apelin-13 was recently proposed as an alternative to the recommended β-adrenergic drugs for supporting endotoxin-induced myocardial dysfunction. Since Apelin-13 signals through its receptor (Apelin peptide jejunum) to exert singular inotropic/vasotropic actions and to optimize body fluid balance, this candidate pathway might benefit septic shock management. Whether the newly discovered ELABELA (ELA), a second endogenous ligand of the Apelin peptide jejunum receptor highly expressed in the kidney, further improves cardio-renal impairment remains unknown...
August 2, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28751956/saponins-as-adipokines-modulator-a-possible-therapeutic-intervention-for-type-2-diabetes
#7
REVIEW
Olusola Olalekan Elekofehinti, Oluwamodupe Cecilia Ejelonu, Jean Paul Kamdem, Oluwaseun Benedicta Akinlosotu, Isaac Gbadura Adanlawo
Development of type 2 diabetes has been linked to β-cell failure coupled with insulin resistance and obesity. Adipose tissue, known as the fat store, secretes a number of hormones and proteins collectively termed adipokines some of which regulate insulin sensitivity. Dysregulation in the secretion of adipokines has been linked to insulin resistance and type 2 diabetes. In this review, we summarized evidence of the role of adipokines with focus on leptin, adiponectin, adipsin, visfatin and apelin in the pathogenesis of type 2 diabetes and discussed the potential of saponins to modify the ill-regulated adipokines secretions, which could promote the use of this class of phytochemicals as potential antidiabetics agents...
July 15, 2017: World Journal of Diabetes
https://www.readbyqxmd.com/read/28748915/the-endoplasmic-reticulum-stress-autophagy-pathway-is-involved-in-apelin-13-induced-cardiomyocyte-hypertrophy-in-vitro
#8
Feng Xie, Di Wu, Shi-Fang Huang, Jian-Gang Cao, He-Ning Li, Lu He, Mei-Qing Liu, Lan-Fang Li, Lin-Xi Chen
Apelin is the endogenous ligand for the G protein-coupled receptor APJ, and plays important roles in the cardiovascular system. Our previous studies showed that apelin-13 promotes the hypertrophy of H9c2 rat cardiomyocytes through the PI3K-autophagy pathway. The aim of this study was to explore what roles ER stress and autophagy played in apelin-13-induced hypertrophy of cardiomyocytes in vitro. Treatment of H9c2 cells with apelin-13 (0.001-2 μmol/L) dose-dependently increased the production of ROS and the expression levels of NADPH oxidase 4 (NOX4)...
July 27, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28748611/apelin-induced-cardioprotection-against-ischemia-reperfusion-injury-roles-of-epidermal-growth-factor-and-src
#9
Anna Folino, Lisa Accomasso, Claudia Giachino, Pier Giorgio Montarolo, Gianni Losano, Pasquale Pagliaro, Raffaella Rastaldo
AIM: Apelin, the ligand of the G-protein-coupled-receptor (GPCR) APJ, exerts a postconditioning-like protection against ischemia-reperfusion injury through activation of PI3K-Akt-NO signalling. The pathway connecting APJ to PI3K is still unknown. Since other GPCR ligands act through transactivation of epidermal growth factor receptor (EGFR) via a matrix-metalloproteinase (MMP) or Src kinase, we investigated whether EGFR transactivation is involved in the following three features of apelin-induced cardioprotection: limitation of infarct size, suppression of contracture, and improvement of post-ischemic contractile recovery...
July 27, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28736029/protective-role-of-apelin-against-cyclosporine-induced-renal-tubular-injury-in-rats
#10
J S Kim, J W Yang, B G Han, H J Kwon, J H Kim, S O Choi
BACKGROUND: Cyclosporine (CsA) usually reduces glomerular filtration rate (GFR) but also can induce tubular injury without resulting in GFR reduction. Apelin is an endogenous ligand for the apelin receptor and has diverse physiologic roles related to hemodynamic or metabolic processes. We investigated the renoprotective role of apelin against CsA-induced tubular toxicity in rats. METHODS: Rats were given CsA (15 mg/kg/day) and/or apelin-13 (15 μg/kg/day) for 7 days via subcutaneous injection...
July 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28730728/beneficial-long-term-antidiabetic-actions-of-n-and-c-terminally-modified-analogues-of-apelin-13-in-diet-induced-obese-diabetic-mice
#11
V Parthsarathy, C Hogg, P R Flatt, F P M O'Harte
AIMS: This study investigated the chronic effects of twice daily administration of stable apelin analogues, apelin-13 amide and (pGlu)apelin-13 amide, on metabolic parameters in glucose intolerant and insulin resistant diet-induced obese (DIO) mice fed a high-fat diet for 150 days. STUDY DESIGN & METHODS: Groups of mice received twice daily (09:00 and 17:00 h) injections of saline vehicle, apelin-13 amide, (pGlu)apelin-13 amide or exendin-4(1-39) for 28 days (all at 25 nmol/kg)...
July 20, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28728608/influence-of-apelin-12-on-troponin-levels-and-the-rate-of-mace-in-stemi-patients
#12
Xhevdet Krasniqi, Blerim Berisha, Masar Gashi, Dardan Koçinaj, Fisnik Jashari, Josip Vincelj
BACKGROUND: During acute myocardial infarction, phosphorylated TnI levels, Ca(2+) sensitivity and ATPase activity are decreased in the myocardium, and the subsequent elevation in Ca(2+) levels activates protease I (caplain I), leading to the proteolytic degradation of troponins. Concurrently, the levels of apelin and APJ expression are increased by limiting myocardial injury. METHODS: In this prospective observational study, 100 consecutive patients with ST-elevation acute myocardial infarction were included...
July 20, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/28712823/an-overview-on-biological-functions-and-emerging-therapeutic-roles-of-apelin-in-diabetes-mellitus
#13
REVIEW
Farzaneh Ghafarian Alipour, Mohamad Reza Ashoori, Younes Pilehvar-Soltanahmadi, Nosratollah Zarghami
Type 2 diabetes mellitus is a common type of diabetes and considered as multifactorial disease. Apelin is an adipokine which secreted from white adipose tissue and involved in various functions such as insulin sensitivity and food intake. Many studies showed that apelin has a crucial role in diabetes and its concentration will change in relation with insulin resistance. In this review, we will discuss the roles of apelin in energy metabolism and pathogenesis of diabetes and explain why apelin can be a good candidate adipokine to promoting insulin sensitivity...
July 4, 2017: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/28710384/prospective-evaluation-of-the-diagnostic-value-of-plasma-apelin-12-levels-for-differentiating-patients-with-moyamoya-and-intracranial-atherosclerotic-diseases
#14
Wei Hu, Wan Jiang, Li Ye, Yanghua Tian, Bing Shen, Kai Wang
Patients with moyamoya disease (MMD) or intracranial atherosclerotic disease (ICAD) experience similar cerebral ischaemic events. However, MMD patients show greater angiogenesis and arteriogenesis, which play crucial roles in collateral circulation development to enhance clinical prognosis and outcome. Apelins have been associated with angiogenesis and arteriogenesis. Therefore, the aim of the present study was to determine whether apelin levels were higher in patients with MMD than in patients with ICAD or in healthy controls...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28690216/-plasma-level-of-apelin-and-carotid-atherosclerosis-in-maintenance-hemodialysis-patients
#15
Rong Tang, Ruiling Wang, Xiang Ao, Xiaomiao Cheng
To determine the plasma level of apelin in patients of maintenance hemodialysis (MHD) and to explore the relationship between apelin level and carotid atherosclerosis (AS) in MHD patients.
 Methods: A total of 92 MHD patients and 36 sex- and age-matched healthy subjects were enrolled in this study. The plasma level of apelin was evaluated by radiation immunoassay; serum endothelial injury markers including thrombomodulin, von Willebrand factor (vWF), and CD146, and inflammatory factors including high sensitive C-reactive protein (hsCRP), IL-6 and TNF-α were determined by ELISA...
June 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/28685579/synthetic-modification-within-the-rprl-region-of-apelin-peptides-impact-on-cardiovascular-activity-and-stability-to-neprilysin-and-plasma-degradation
#16
Shaun M K McKinnie, Wang Wang, Conrad Fischer, Tyler McDonald, Kevin R Kalin, Xavier Iturrioz, Catherine Llorens-Cortes, Gavin Y Oudit, John C Vederas
Apelin is an important mammalian peptide hormone with a range of physiological roles, especially in the cardiovascular system. The apelinergic system is a promising target for treatment of disease, but this remains to be realized due to rapid proteolysis of apelin-derived peptides by proteases, including neprilysin (NEP). The synthetic analogues modified within the NEP degradation site ("RPRL" motif) showed improved in vitro proteolytic stability while maintaining receptor-binding affinities, with three candidate peptides retaining full cardiovascular activities for potential therapeutic application...
July 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28681996/apelin-administration-improves-insulin-sensitivity-in-overweight-men-during-an-hyperinsulinemic-euglycemic-clamp
#17
Pierre Gourdy, Laurent Cazals, Claire Thalamas, Agnès Sommet, Fabienne Calvas, Monique Galitzky, Claire Vinel, Cédric Dray, Hélène Hanaire, Isabelle Castan-Laurell, Philippe Valet
AIMS: Apelin is a recently identified adipokine known to improve glucose tolerance and insulin sensitivity in murine models. This study was dedicated to the proof of concept that apelin administration also enhances insulin sensitivity in humans. MATERIALS AND METHODS: Healthy overweight men were enrolled in this randomized, double-blind, placebo-controlled, cross-over study that successively considered the efficacy and the tolerance of two doses of (pyr1)-Apelin-13...
July 6, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28663440/elabela-deficiency-promotes-preeclampsia-and-cardiovascular-malformations-in-mice
#18
Lena Ho, Marie Van Dijk, Sam Tan Jian Chye, Daniel M Messerschmidt, Serene C Chng, Sheena Ong, Ling Ka Yi, Souad Boussata, Grace Hui-Yi Goh, Gijs B Afink, Chin Yan Lim, N Ray Dunn, Davor Solter, Barbara B Knowles, Bruno Reversade
Pre-eclampsia (PE) is a gestational hypertensive syndrome affecting between 5 and 8% of all pregnancies. While PE is the leading cause of fetal and maternal morbidity/mortality, its molecular etiology is still unclear. Here, we show that ELABELA (ELA), an endogenous ligand of the apelin receptor (APLNR, or APJ), is a circulating hormone secreted by the placenta. Elabela but not Apelin knockout pregnant mice exhibit PE-like symptoms, including proteinuria and elevated blood pressure due to defective placental angiogenesis...
June 29, 2017: Science
https://www.readbyqxmd.com/read/28653788/mir-497-accelerates-oxidized-low-density-lipoprotein-induced-lipid-accumulation-in-macrophages-by-repressing-the-expression-of-apelin
#19
Junfeng Cui, Zhong Ren, Wenshuang Zou, Yanling Jiang
microRNAs (miRNAs) play important roles in the pathogenesis of atherosclerosis. A previous study has reported that miR-497 is elevated in advanced atherosclerotic lesions in an apoE-deficient (apoE-/-) mouse model. The purpose of this study is to test whether miR-497 can modulate macrophage foam cell formation, an initiating event in atherosclerosis. We found that miR-497 was upregulated in THP-1 macrophages after treatment with oxidized low-density lipoprotein (oxLDL). Enforced expression of miR-497 promoted lipid accumulation and decreased cholesterol efflux in oxLDL-exposed THP-1 macrophages...
June 27, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28653126/impact-of-metabolic-hormones-secreted-in-human-breast-milk-on-nutritional-programming-in-childhood-obesity
#20
REVIEW
Pilar Amellali Badillo-Suárez, Maricela Rodríguez-Cruz, Xóchitl Nieves-Morales
Obesity is the most common metabolic disease whose prevalence is increasing worldwide. This condition is considered a serious public health problem due to associated comorbidities such as diabetes mellitus and hypertension. Perinatal morbidity related to obesity does not end with birth; this continues affecting the mother/infant binomial and could negatively impact on metabolism during early infant nutrition. Nutrition in early stages of growth may be essential in the development of obesity in adulthood, supporting the concept of "nutritional programming"...
June 27, 2017: Journal of Mammary Gland Biology and Neoplasia
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