Immunohistochemical distribution of the secretogranin II-derived peptide EM66 in the rat hypothalamus: A comparative study with jerboa

Boutahricht, M.; Guillemot, Johann; Montero-Hadjadje, Maïté; Barakat, Youssef; Ouezzani, Seloua El; Alaoui, Abdelilah Lamrani; Yon, Laurent; Vaudry, Hubert; Anouar, Youssef; Magoul, Rabia

doi:10.1016/j.neulet.2006.12.033

Cited by 15 publications

(15 citation statements)

References 21 publications

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“…EM66 was named according to its length (66 amino acids) and its N‐ and C‐terminal glutamic acid and methionine residues, respectively, in the human sequence . EM66 was initially characterised in the human adrenal gland, in gonadotrophs and lactotrophs of the rat pituitary, and in specific rodent hypothalamic nuclei, suggesting that, upon stimulation, EM66 may be released to act as an autocrine, paracrine and/or endocrine factor . Clinically, it has been shown that EM66 is present in tumoural chromaffin cells and represents a sensitive diagnostic and pronostic marker of pheochromocytoma .…”

Section: Introductionmentioning

confidence: 99%

“…Neuroanatomical studies have revealed that, in the jerboa, EM66‐producing neurones are present in various hypothalamic structures, including the suprachiasmatic, supraoptic, parvocellular paraventricular (pPVN) and arcuate (ARC) nuclei, and the lateral hypothalamic area (LHA) . Similarly, in the rat hypothalamus, EM66‐containing neurones are found in the pPVN, preoptic area, ARC and in the LHA .…”

Section: Introductionmentioning

confidence: 99%

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A potential role for the secretogranin II‐derived peptide EM66 in the hypothalamic regulation of feeding behaviour

Trebak

Dubuc

Arabo

et al. 2017

J Neuroendocrinology

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EM66 is a conserved 66-amino acid peptide derived from secretogranin II (SgII), a member of the granin protein family. EM66 is widely distributed in secretory granules of endocrine and neuroendocrine cells, as well as in hypothalamic neurones. Although EM66 is abundant in the hypothalamus, its physiological function remains to be determined. The present study aimed to investigate a possible involvement of EM66 in the hypothalamic regulation of feeding behaviour. We show that i.c.v. administration of EM66 induces a drastic dose-dependent inhibition of food intake in mice deprived of food for 18 hours, which is associated with an increase of hypothalamic pro-opiomelanocortin (POMC) and melanocortin-3 receptor mRNA levels and c-Fos immunoreactivity in the POMC neurones of the arcuate nucleus. By contrast, i.c.v. injection of EM66 does not alter the hypothalamic expression of neuropeptide Y (NPY), or that of its Y1 and Y5 receptors. A 3-month high-fat diet (HFD) leads to an important decrease of POMC and SgII mRNA levels in the hypothalamus, whereas NPY gene expression is not affected. Finally, we show that a 48 hours of fasting in HFD mice decreases the expression of POMC and SgII mRNA, which is not observed in mice fed a standard chow. Taken together, the present findings support the view that EM66 is a novel anorexigenic neuropeptide regulating hypothalamic feeding behaviour, at least in part, by activating the POMC neurones of the arcuate nucleus.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A potential role for the secretogranin II‐derived peptide EM66 in the hypothalamic regulation of feeding behaviour

Trebak

Dubuc

Arabo

et al. 2017

J Neuroendocrinology

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“…Additionally, pig SCG2 has nine pairs of dibasic sites that are potential cleavage sites in the posttranslational modifications by endoproteolytic enzymes (Muller et al 1997), which is consistent with those of the other homologs, such as rat (Gerdes et al 1988), human (Gerdes et al 1989), and ox (Fischer-Colbrie et al 1990). Previously, two secretogranin II-derived peptides, SN and EM66, have been identified from human, rat, and jerboa and have been widely studied (Anouar et al 1998;Montero-Hadjadje et al 2003;Boutahricht et al 2005Boutahricht et al , 2007Zhao et al 2006;Guillemot et al 2006), and manserin, another neuropeptide of 40 amino acids from secretogranin II, has also been isolated recently from the rat in the neuroendocrine system (Yajima et al 2004). Putative pig SN, EM66, and manserin were indicated in the present study based on those sequences from human and rat (Anouar et al 1998;Yajima et al 2004).…”

Section: Discussionmentioning

confidence: 62%

Molecular Cloning, Mapping, and Polymorphism of the Porcine SCG2 gene

Chen

Zhang

et al. 2008

Biochem Genet

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The secretogranin II (SCG2) gene is associated with the synthesis and secretion of follicle-stimulating hormone and luteinizing hormone. In the present study, we have determined the complete cDNA sequence of pig SCG2, which was submitted to GenBank with accession no. AY870646. Its complete open reading frame of 1,851 nucleotides encodes 616 amino acids. The predicted protein shares 80-87% identity with mouse, human, and bovine SCG2 proteins, and all four species share almost complete identity in the secretoneurin and EM66 domains. Pig SCG2 is a protein of 589 amino acids and 68,132 Da, preceded by a signal peptide of 27 residues. It contains nine pairs of dibasic residues, which are used as potential cleavage sites for generation of physiologically active peptides. Analysis of the SCG2 gene across the INRA-Minnesota porcine radiation hybrid panel indicates close linkage with microsatellite marker SW2608, located on Sus scrofa chromosome 15 (SSC15) q25, which harbors several QTL for ovulation rate and meat quality. Comparative sequencing and EST analysis revealed nine SNPs in porcine SCG2 cDNA, including seven SNPs in the coding region and two SNPs in the 3' UTR. Four nonsynonymous SNPs (G622A, G1671T, C1718T, and A1790C) resulted in amino acid substitutions of Ala-->Thr, Glu-->Asp, Pro-->Leu, and Asn-->Thr, respectively.

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“…In particular, the sequence of human secretogranin II (SgII or SCG2 as given in the HUGO database) contains nine pairs of basic amino acids that represent potential cleavage sites by PCs. Indeed, proteolytic processing of SgII leads to the production of several peptides, such as secretoneurin (SN; SgII 152-184 ) which regulates neurotransmission, inflammatory responses, and gonadotrope activity (Fischer-Colbrie et al 2005, Shyu et al 2008, Zhao et al 2010; EM66 (SgII ) which may participate in the control of feeding behavior in rodents (Boutahricht et al 2005(Boutahricht et al , 2007; and manserin ) whose putative role remains to be established (Yajima et al 2004, Tano et al 2010. The ubiquitous distribution of granins and their derived peptides in nervous, endocrine, and neuroendocrine tissues makes these entities useful markers of secretion from neuroendocrine cells and neoplasms (Rosa & Gerdes 1994).…”

Section: Introductionmentioning

confidence: 99%

Differential expression and processing of secretogranin II in relation to the status of pheochromocytoma: implications for the production of the tumoral marker EM66

Guillemot¹,

Thouennon²,

Guérin³

et al. 2012

Journal of Molecular Endocrinology

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We have previously demonstrated that measurement of tissue concentrations of the secretogranin II (SgII or SCG2 as listed in the HUGO database)-derived peptide EM66 may help to discriminate between benign and malignant pheochromocytomas and that EM66 represents a sensitive plasma marker of pheochromocytomas. Here, we investigated the gene expression and protein production of SgII in 13 normal adrenal glands, and 35 benign and 16 malignant pheochromocytomas with the goal to examine the molecular mechanisms leading to the marked variations in the expression of EM66 in tumoral chromaffin tissue. EM66 peptide levels were 16-fold higher in benign than in malignant pheochromocytomas and had an area under the receiver-operating characteristic curve of 0 . 95 for the distinction of benign and malignant tumors. Q-PCR experiments indicated that the SgII gene was significantly underexpressed in malignant tumors compared with benign tumors. Western blot analysis using antisera directed against SgII and SgII-derived fragments revealed lower SgII protein and SgII-processing products in malignant tumors. Western blot also showed that low p-cAMP-responsive element-binding (CREB) concentrations seemed to be associated with the malignant status. In addition, the prohormone convertase PC1 and PC2 genes and proteins were overexpressed in benign pheochromocytomas compared with malignant pheochromocytomas. Low concentrations of EM66 found in malignant tumors are associated with reduced expression and production of SgII and SgII-derived peptides that could be ascribed to a decrease in SgII gene transcription, probably linked to p-CREB down-regulation, and to lower PC levels. These findings highlight the mechanisms leading to lower concentrations of EM66 in malignant pheochromocytoma and strengthen the notion that this peptide is a suitable marker of this neuroendocrine tumor.

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Immunohistochemical distribution of the secretogranin II-derived peptide EM66 in the rat hypothalamus: A comparative study with jerboa

Cited by 15 publications

References 21 publications

A potential role for the secretogranin II‐derived peptide EM66 in the hypothalamic regulation of feeding behaviour

A potential role for the secretogranin II‐derived peptide EM66 in the hypothalamic regulation of feeding behaviour

Molecular Cloning, Mapping, and Polymorphism of the Porcine SCG2 gene

Differential expression and processing of secretogranin II in relation to the status of pheochromocytoma: implications for the production of the tumoral marker EM66

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