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Yuanlin Dong, Madhu Chauhan, Michael Belfort, Chandra Yallampalli
Calcitonin gene-related peptide (CALCB), adrenomedullin (ADM) and adrenomedullin 2 (ADM2)/intermedin (IMD) play critical roles in vascular adaptation during pregnancy through calcitonin-receptor-like-receptor (CALCRL) and receptor activity-modifying proteins (RAMPs). This study was designed to assess the predominant RAMP that associates with CALCRL to form a functional receptor in the rat uterine artery smooth muscle (RUASM). We also determined if these receptor component associations are decreased by TNF-α and if CALCB, ADM or ADM2 can rescue CRLR/RAMP associations...
October 26, 2016: Biology of Reproduction
Aichurek Soultanova, Zbigniew Mikulski, Uwe Pfeil, Veronika Grau, Wolfgang Kummer
Members of the calcitonin peptide family-calcitonin gene-related peptide (CGRP), adrenomedullin (AM), and adrenomedullin2/intermedin (IMD)-exert modulatory effects upon monocytes and macrophages of various extrapulmonary origins. Utilizing the rat alveolar macrophage (AMφ) cell line NR8383, we here set out to determine to which extent these three peptides and their receptors are differentially regulated in AMφ and what specific effects they have on AMφ key functions. LPS treatment differentially up-regulated expression of the peptides and receptors...
2016: PloS One
Wei-Wei Lu, Li-Xin Jia, Xian-Qiang Ni, Lei Zhao, Jin-Rui Chang, Jin-Sheng Zhang, Yue-Long Hou, Yi Zhu, You-Fei Guan, Yan-Rong Yu, Jie Du, Chao-Shu Tang, Yong-Fen Qi
OBJECTIVE: Oxidative stress plays a critical role in the development of abdominal aortic aneurysm (AAA). Intermedin (IMD) is a regulator of oxidative stress. Here, we investigated whether IMD reduces AAA by inhibiting oxidative stress. APPROACH AND RESULTS: In angiotensin II-induced ApoE(-)(/-) mouse and CaCl2-induced C57BL/6J mouse model of AAA, IMD1-53 significantly reduced the incidence of AAA and maximal aortic diameter. Ultrasonography, hematoxylin, and eosin staining and Verhoeff-van Gieson staining showed that IMD1-53 significantly decreased the enlarged aortas and elastic lamina degradation induced by angiotensin II or CaCl2...
November 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Madhu Chauhan, Meena Balakrishnan, Alex Vidaeff, Uma Yallampalli, Fernando Lugo, Karin Fox, Michael Belfort, Chandra Yallampalli
CONTEXT: It is not known whether decreases in trophoblast invasion promoting the peptide, adrenomedullin2 (ADM2) system is associated with preeclampsia (PreE). OBJECTIVE: The objective of the study was to assess the changes in ADM2 levels in plasma, placenta, and amniotic fluid (AF) and its receptor components in placenta from PreE pregnancy compared with the age-matched normal and study the effect of ADM2 on the synthesis of nitric oxide (NO), endothelial nitric oxide synthase (eNOS), and matrix-metalloproteinase (MMP)-2 and MMP-9 in trophoblast cells...
November 2016: Journal of Clinical Endocrinology and Metabolism
Cathryn Weston, Ian Winfield, Matthew Harris, Rose Hodgson, Archna Shah, Simon J Dowell, Juan Carlos Mobarec, David A Woodlock, Christopher A Reynolds, David R Poyner, Harriet A Watkins, Graham Ladds
The calcitonin gene-related peptide (CGRP) family of G protein-coupled receptors (GPCRs) is formed through the association of the calcitonin receptor-like receptor (CLR) and one of three receptor activity-modifying proteins (RAMPs). Binding of one of the three peptide ligands, CGRP, adrenomedullin (AM), and intermedin/adrenomedullin 2 (AM2), is well known to result in a Gαs-mediated increase in cAMP. Here we used modified yeast strains that couple receptor activation to cell growth, via chimeric yeast/Gα subunits, and HEK-293 cells to characterize the effect of different RAMP and ligand combinations on this pathway...
October 14, 2016: Journal of Biological Chemistry
Uwe Pfeil, Subhashini Bharathala, Ghulam Murtaza, Petra Mermer, Tamara Papadakis, Andreas Boening, Wolfgang Kummer
Heart valves are highly organized structures determining the direction of blood flow through the heart. Smooth muscle cells within the valve are thought to play an active role during the heart cycle, rather than being just passive flaps. The mature heart valve is composed of extracellular matrix (ECM), various differentiations of valvular interstitial cells (VIC), smooth muscle cells and overlying endothelium. VIC are important for maintaining the structural integrity of the valve, thereby affecting valve function and ECM remodelling...
August 23, 2016: Cell and Tissue Research
Tao Li, Zhu Yu, Wu Huiling, Wu Yue, Zhang Jie, Peng Xiaoyong, Zang Jiatao, Xiang Xinming, Liangming Liu
OBJECTIVE: Intermedin (IMD) is a calcitonin gene-related peptide shown to have a protective effect on myocardial function in ischemia-reperfusion injury. Whether IMD has beneficial effect in severe sepsis and septic shock (and its underlying mechanisms) is not known. METHODS: We induced septic shock using cecal ligation and puncture (CLP). We focused on the potential beneficial effect of IMD1-53 on cardiac papillary muscle and cardiomyocytes against septic shock and its relationship with protection of cardiac function...
June 28, 2016: Shock
Lih-Geeng Chen, Pei-Jung Su, Po-Wei Tsai, Ling-Ling Yang, Ching-Chiung Wang
Eight ethanolic extracts of indigenous Taiwanese plants of the genus Alpinia were tested for tumor cytotoxicity against AGS, Hep G2, HeLa, KB, and HL-60 cells. Among the 50 % and 95 % EtOH extracts of eight Alpinia species, the cytotoxic effects of Alpinia intermedia leaves were the strongest. When the leaf extract of A. intermedia was partitioned using n-hexane and aqueous solvents, the n-hexane layer showed a greater cytotoxic effect and could prolong the survival time of P-388D1 tumor-bearing CDF1 mice...
June 28, 2016: Planta Medica
S Martínez-Herrero, A Martínez
Adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) are 2 biologically active peptides produced by the same gene, ADM, with ubiquitous distribution and many physiological functions. Adrenomedullin is composed of 52 amino acids, has an internal molecular ring composed by 6 amino acids and a disulfide bond, and shares structural similarities with calcitonin gene-related peptide, amylin, and intermedin. The AM receptor consists of a 7-transmembrane domain protein called calcitonin receptor-like receptor in combination with a single transmembrane domain protein known as receptor activity-modifying protein...
July 2016: Domestic Animal Endocrinology
Irina E Kovaleva, Alisa A Garaeva, Peter M Chumakov, Alexandra G Evstafieva
Intermedin or adrenomedullin 2 is a set of calcitonin-related peptides with a putative tumor angiogenesis promoting activity that are formed by proteolytic processing of the ADM2 gene product. It has been proposed that the ADM2 gene is regulated by the estrogen response element (ERE) and hypoxia response elements (HRE) found within its promoter region. In the present study we reveal a functional mechanism by which ADM2 participates in the unfolded protein response (UPR) and in responses to the mitochondrial respiration chain inhibition...
September 15, 2016: Gene
Madhu Chauhan, Ancizar Betancourt, Meena Balakrishnan, Uma Yallampalli, Yuanlin Dong, Karin Fox, Michael Belfort, Chandra Yallampalli
RATIONALE: Calcitonin gene-related peptide (CGRP), adrenomedullin (ADM), and adrenomedullin2 (ADM2)/intermedin are potent vasorelaxant peptides considered to play a role in the adaptive mechanisms in rat pregnancy through increased vasodilation in mesenteric and uterine artery. OBJECTIVE: This study was designed to demonstrate the response of omental arteries (OA) to vasoactive peptides CGRP, ADM, and ADM2 in pregnancy complications such as fetal growth restriction (FGR), and assess the changes in the expression of their receptor components in segments of OA from FGR pregnancy compared to the control...
August 2016: Journal of Clinical Endocrinology and Metabolism
Pengyang Li, Lin Shi, Yalei Han, Yuntao Zhao, Yongfen Qi, Bin Wang
Intermedin (IMD), an autocrine/paracrine biologically active peptide, plays a critical role in maintaining vascular homeostasis. Recent research has shown that high plasma levels of IMD are associated with poor outcomes for patients with ST-segment elevation acute myocardial infarction. However, the prognostic utility of IMD levels in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) has not yet been investigated. We hypothesized that the level of plasma IMD would have prognostic value in patients with NSTE-ACS...
April 2016: Medicine (Baltimore)
Yanli Pang, Yang Li, Ying Lv, Lulu Sun, Songyang Zhang, Yin Li, Yuhui Wang, George Liu, Ming-Jiang Xu, Xian Wang, Changtao Jiang
Hyperhomocysteinemia (HHcy) is a condition characterized by an abnormally high level of homocysteine, an inflammatory factor. This condition has been suggested to promote insulin resistance. To date, the underlying molecular mechanism remains largely unknown, and identifying novel therapeutic targets for HHcy-induced insulin resistance is of high priority. It is well known that intermedin (IMD), a calcitonin family peptide, exerts potent anti-inflammatory effects. In this study, the effects of IMD on HHcy-induced insulin resistance were investigated...
June 3, 2016: Journal of Biological Chemistry
Qingtao Meng, Di Shi, Jiayue Feng, Yanling Su, Yang Long, Sen He, Si Wang, Yong Wang, Xiangxun Zhang, Xiaoping Chen
OBJECTIVE: Hypercholesterolemia can cause damage to the artery. Intermedin (IMD) is a novel member of the calcitonin gene-related peptide family. This study aims to investigate the aortic expression of IMD and its receptors in hypercholesterolemia without atherosclerosis. METHODS: Male Wistar rats were fed with high cholesterol diet, with or without simvastatin and vitamin C. Both the malondialdehyde (MDA) and superoxide dismutase (SOD) in plasma and aorta were determined as the oxidative stress biomarkers...
2016: Annals of Clinical and Laboratory Science
Emmanuel Letsyo, Gerold Jerz, Peter Winterhalter, Gert Horn, Till Beuerle
INTRODUCTION: Growing demand for heart-healthy omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is putting stress on wild fish stocks. There is now a compelling need for new and novel sources of non-traditional seed oils containing high stearidonic acid (SDA), a precursor of EPA and DHA, to reduce this demand. The seed oil of Lappula squarrosa is one of the richest sources of SDA, however, the plant has been found to contain toxic pyrrolizidine alkaloids (PAs)...
March 2016: Phytochemical Analysis: PCA
Jin Rui Chang, Jun Guo, Yue Wang, Yue Long Hou, Wei Wei Lu, Jin Sheng Zhang, Yan Rong Yu, Ming Jiang Xu, Xiu Ying Liu, Xiu Jie Wang, You Fei Guan, Yi Zhu, Jie Du, Chao Shu Tang, Yong Fen Qi
Deficiency in α-Klotho is involved in the pathogenesis of vascular calcification. Since intermedin (IMD)1-53 (a calcitonin/calcitonin gene-related peptide) protects against vascular calcification, we studied whether IMD1-53 inhibits vascular calcification by upregulating α-Klotho. A rat model of chronic kidney disease (CKD) with vascular calcification induced by the 5/6 nephrectomy plus vitamin D3 was used for study. The aortas of rats with CKD showed reduced IMD content but an increase of its receptor, calcitonin receptor-like receptor, and its receptor modifier, receptor activity-modifying protein 3...
March 2016: Kidney International
H Zhang, S-Y Zhang, C Jiang, Y Li, G Xu, M-J Xu, X Wang
OBJECTIVES: There is an urgent need to develop interventions and policies to mitigate the health effects of obesity by targeting its metabolic mediators. Adrenomedullin 2 (AM2)/intermedin (IMD) is a secreted peptide that has an important role in protecting the cardiovascular system. However, the role of AM2 in type 2 diabetes is unknown. METHODS: Wild-type (WT) and aP2/AM2 transgenic (aAM2-tg) mice were fed a high-fat diet (HFD) for 8 weeks, and WT mice were treated with AM2 through mini-osmotic pumps...
May 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
David Bell, Brian J Gordon, Anita Lavery, Katie Megaw, Michael O Kinney, Mark T Harbinson
Intermedin/adrenomedullin-2 (IMD) is a member of the adrenomedullin/CGRP peptide family. Less is known about the distribution of IMD than for other family members within the mammalian cardiovascular system, particularly in humans. The aim was to evaluate plasma IMD levels in healthy subjects and patients with chronic heart failure. IMD and its precursor fragments, preproIMD(25-56) and preproIMD(57-92), were measured by radioimmunoassay in 75 healthy subjects and levels of IMD were also compared to those of adrenomedullin (AM) and mid-region proadrenomedullin(45-92) (MRproAM(45-92)) in 19 patients with systolic heart failure (LVEF<45%)...
February 2016: Peptides
David Bell, Malcolm Campbell, Stephen F McAleer, Matthew Ferguson, Liz Donaghy, Mark T Harbinson
Application of intermedin/adrenomedullin-2 (IMD/AM-2) protects cultured human cardiac vascular cells and fibroblasts from oxidative stress and simulated ischaemia-reoxygenation injury (I-R), predominantly via adrenomedullin AM1 receptor involvement; similar protection had not been investigated previously in human cardiomyocytes (HCM). Expression of IMD, AM and their receptor components was studied in HCM. Receptor subtype involvement in protection by exogenous IMD against injury by simulated I-R was investigated using receptor component-specific siRNAs...
February 2016: Peptides
Peng Wei, Xiang-Jun Yang, Qiang Fu, Bing Han, Lin Ling, Jie Bai, Bin Zong, Chun-Ying Jiang
Intermedin is a proopiomelanocortin-derived peptide before opioid promoting cortical hormone, its main function embodies in mononuclear macrophages and neutrophilic granulocytes to inhibit the proinflammatory cytokines. The aim of this study is to determine intermedin attenuates myocardial infarction and its related mechanisms in a rat model of ischemic heart failure. After rat model of ischemic heart failure was set up, myocardial infarction, blood levels of activities of creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT) were effectively reduced by treatment with intermedin...
2015: International Journal of Clinical and Experimental Pathology
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