scholarly journals Comparison of human and murine enteroendocrine cells by transcriptomic and peptidomic profiling

2018 ◽  
Author(s):  
Geoffrey P Roberts ◽  
Pierre Larraufie ◽  
Paul Richards ◽  
Richard G Kay ◽  
Sam G Galvin ◽  
...  

AbstractEnteroendocrine cells (EECs) produce hormones that regulate food absorption, insulin secretion and appetite. Both EECs and their peptide products are foci of drug discovery programmes for diabetes and obesity. We compared the human and mouse EEC transcriptome and peptidome to validate mouse as a model of the human enteroendocrine axis. We present the first RNA sequencing analysis of human EECs, and demonstrate strong correlation with mouse, although with outliers including some low abundance G-protein coupled receptors. Liquid chromatography mass spectrometry (LC-MS) identified peptide hormone gradients along the human and mouse gut that should enhance progress in gut physiology and therapeutics.


2006 ◽  
Vol 49 (5) ◽  
pp. 515-516
Author(s):  
C. L. Zhang ◽  
H. Chen ◽  
Y. H. Wang ◽  
X. Y. Lan ◽  
L. Zhang ◽  
...  

Abstract. Melanocortin-4 receptor (MC4R) is one of five G-protein-coupled receptors binding melanocortins that is implicated in the control of ingestive behavior and energy homeostasis. Mutations have been described in the human and mouse MC4R genes which are associated with obesity (YEO et al., 1998; HUSZAR et al., 1997). Moreover, a mutation in porcine MC4R is associated with economically important traits in the pig (KIM et al., 2000). The SNPs reported in bovine MC4R coding region were specific to breeds (VALLE et al., 2004; THUE et al., 2001; HAEGEMAN et al., 2001). In the present experiment over 95% of the coding region of MC4R were screened to detect the SNPs in the predominant cattle breeds of China. Association of a missense mutation of MC4R gene with growth traits was analyzed.



Genomics ◽  
2006 ◽  
Vol 88 (3) ◽  
pp. 263-273 ◽  
Author(s):  
Thóra K. Bjarnadóttir ◽  
David E. Gloriam ◽  
Sofia H. Hellstrand ◽  
Helena Kristiansson ◽  
Robert Fredriksson ◽  
...  


Genomics ◽  
2004 ◽  
Vol 84 (1) ◽  
pp. 23-33 ◽  
Author(s):  
Thóra K. Bjarnadóttir ◽  
Robert Fredriksson ◽  
Pär J. Höglund ◽  
David E. Gloriam ◽  
Malin C. Lagerström ◽  
...  


2007 ◽  
Vol 35 (4) ◽  
pp. 717-720 ◽  
Author(s):  
M. Wheatley ◽  
J. Simms ◽  
S.R. Hawtin ◽  
V.J. Wesley ◽  
D. Wootten ◽  
...  

GPCRs (G-protein-coupled receptors) are a large family of structurally related proteins which mediate their effects by coupling to G-proteins. The V1aR (V1a vasopressin receptor) is a member of a family of related GPCRs that are activated by vasopressin {AVP ([Arg8]vasopressin)}, OT (oxytocin) and related peptides. These receptors are members of a subfamily of Family A GPCRs called the neurohypophysial peptide hormone receptor family. GPCRs exhibit a conserved tertiary structure comprising a bundle of seven TM (transmembrane) helices linked by alternating ECLs (extracellular loops) and ICLs (intracellular loops). The cluster of TM helices is functionally important for ligand binding, and, furthermore, activation of GPCRs involves movement of these TM helices. Consequently, it might be assumed that the extracellular face of GPCRs is composed of peptide linkers that merely connect important TM helices. However, using a systematic mutagenesis approach and focusing on the N-terminus and the second ECL of the V1aR, we have established that these extracellular domains fulfil a range of important roles with respect to GPCR signalling, including agonist binding, ligand selectivity and receptor activation.



2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Aya Helmy ◽  
Mohamed El-Shazly ◽  
Nesreen Omar ◽  
Mohamed Rabeh ◽  
Usama Ramadan Abdelmohsen ◽  
...  

Gum Arabic (GA), parsley, and corn silk have been traditionally used for renal failure patients worldwide. This study aimed at probing the mechanism of the combined extracts, namely, GA (3 g/kg/day), parsley (1 g/kg/day), and corn silk (200 mg/kg/day), as nephroprotective agents in mice after amikacin (1.2 g/kg) single dose through exploration of their action on G-protein coupled receptors (GPR) 41 and 43 and the ensuing lysosomal biogenesis. Western blotting was employed for renal levels of bcl-2-associated X protein (BAX) and cytosolic cathepsin D; cell death markers, nuclear transcription factor EB (TFEB), and lysosomal associated membrane protein-1 (LAMP-1); and lysosomal biogenesis indicators. Liquid chromatography–mass spectrometry (LC-MS) and docking were also employed. After amikacin treatment, BAX and cathepsin D levels were upregulated while LAMP-1 and nuclear TFEB levels were inhibited. The combined extracts inhibited BAX and cytosolic cathepsin D but upregulated LAMP-1 and nuclear TFEB levels. Docking confirmed GPR modulatory signaling. The combined extracts showed GPR signal modulatory properties that triggered lysosome synthesis and contributed to reversing the adverse effects of amikacin on renal tissues.



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