Effects of ghrelin and des-acyl ghrelin on neurogenesis of the rat fetal spinal cord

Sato, Miho; Nakahara, Keiko; Goto, Shintaro; Kaiya, Hiroyuki; Miyazato, Minoru; Date, Yukari; Nakazato, Masamitsu; Kangawa, Kenji; Murakami, Noboru

doi:10.1016/j.bbrc.2006.09.088

Cited by 82 publications

(60 citation statements)

References 24 publications

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“…A role in embryonic development, rather than appetite, may be more relevant for ghrelin at hatching. Studies in mammals that support this idea include reports of ghrelin expression in early embryo development (morula cells, Kawamura et al 2003) and ghrelin-mediated induction of fetal neurogenesis (Sato et al 2006).…”

Section: Discussionmentioning

confidence: 98%

“…The effect of ghrelin on GH secretion is comparable with or potentially more potent than the classical hypothalamic regulator, GH-releasing hormone (Kojima et al 1999, Gualillo et al 2006. In addition to appetite and GH secretion, ghrelin has been implicated in other functions involving gastric acid secretion and motility, pancreatic activity and carbohydrate metabolism, prolactin secretion, cardiovascular actions, reproduction, fetal growth and development, as well as effects on apoptosis and cell proliferation (Barreiro & Tena-Sempere 2004, van der Lely et al 2004, Gualillo et al 2006, Sato et al 2006. Recently, evidence has been presented that implicates ghrelin as a signal of energy insufficiency that is able to modulate the endocrine axis regulating reproduction.…”

Section: Introductionmentioning

confidence: 99%

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Ontogenetic and tissue-specific expression of preproghrelin in the Atlantic halibut, Hippoglossus hippoglossus L.

Manning¹,

Murray²,

Gallant³

et al. 2007

Journal of Endocrinology

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Ghrelin is a conserved vertebrate hormone that affects both GH release and appetite. We have cloned and characterized Atlantic halibut preproghrelin cDNA and examined for the first time preproghrelin expression during fish larval development using quantitative real-time PCR. In addition, cellular sites of expression in larvae and tissue-specific expression in 3-year-old halibut were studied. A full-length cDNA for preproghrelin was isolated from halibut stomach tissue. The 899 bp cDNA encodes an open reading frame of 105 amino acids that is comprised of a signal peptide and two peptides with high similarity to ghrelin and obestatin. The deduced amino acid sequence of halibut ghrelin peptide (GSSFLSPSHKPPKGKPPRA) shows significant conservation relative to other teleostean sequences and is identical to human ghrelin for the first seven amino acids of the sequence. The putative obestatin peptide is well-conserved among fishes but shares limited similarity with its human counterpart. Expression of ghrelin was localized to two different cell types in the stomach of larval halibut by in situ hybridization. However, sensitive PCR assays on tissues collected from 3-year-old fish additionally identified ghrelin transcripts in pyloric caecae, intestine, and in immature ovary and testis. Ontogenetic studies detected ghrelin expression prior to exogenous feeding during larval development (hatching and mouth-opening stages) with increased expression occurring through metamorphosis. This increase was pronounced during climax metamorphosis and coincided with stomach differentiation. Patterns of preproghrelin expression suggest that ghrelin has important roles during and after larval development in halibut, and that ghrelin is associated with digestive and gonadal tissues in this teleost.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Ontogenetic and tissue-specific expression of preproghrelin in the Atlantic halibut, Hippoglossus hippoglossus L.

Manning¹,

Murray²,

Gallant³

et al. 2007

Journal of Endocrinology

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“…Ghrelin stimulates the proliferation and inhibits apoptosis of the H9c2 cardiomyocyte cell line [4], human adrenal zona glomerulosa cells [101], preadipocytes [76], osteoblastic cells [96] and pancreatic beta-cells [59] and rat fetal spinal cord [126] and skin cells [108]. Thus, peripheral actions of ghrelin result not only from modulation of function, but also from regulation of survival/proliferation of target cells.…”

Section: Cellular Proliferationmentioning

confidence: 99%

“…Des-acyl promotes cell survival and inhibits apoptosis of H9c2 cardiomyocyte cell line [4] and in pancreatic beta-cells [59]. In vitro, des-acyl ghrelin induces proliferation of rat fetal spinal cord [126] and skin cells [108]. Moreover, des-acyl ghrelin promotes differentiation and fusion of C2C12 skeletal myoblasts [48].…”

Section: Cellular Proliferationmentioning

confidence: 99%

Ghrelin, des-acyl ghrelin and obestatin: Three pieces of the same puzzle

2008

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a b s t r a c tThe major active product of ghrelin gene is a 28-amino acid peptide acylated at the serine 3 position with an octanoyl group, called simply ghrelin. Ghrelin has a multiplicity of physiological functions, affecting GH release, food intake, energy and glucose homeostasis, This suggests the existence of a novel endocrine system with multiple effector elements which not only may have opposite actions but may regulate the action of each other. In this review, we summarize the steps which lead to the production of the different ghrelin gene products and examine the most significant differences between them in terms of structure and actions.

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“…Initially, ghrelin was known to increase neurogenesis in the rat fetal spinal cord (Sato et al 2006) and the nucleus of the solitary tract (Zhang et al 2005) and the dorsal motor nucleus of vagus in adult rats. We previously reported that systemic administration of ghrelin induces hippocampal neurogenesis in adult mice (Moon et al 2009b).…”

Section: Introductionmentioning

confidence: 99%

Multiple signaling pathways mediate ghrelin-induced proliferation of hippocampal neural stem cells

Chung

Kim

et al. 2013

Journal of Endocrinology

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Ghrelin, an endogenous ligand for the GH secretagogue receptor (GHS-R) receptor 1a (GHS-R1a), has been implicated in several physiologic processes involving the hippocampus. The aim of this study was to investigate the molecular mechanisms of ghrelin-stimulated neurogenesis using cultured adult rat hippocampal neural stem cells (NSCs). The expression of GHS-R1a was detected in hippocampal NSCs, as assessed by western blot analysis and immunocytochemistry. Ghrelin treatment increased the proliferation of cultured hippocampal NSCs assessed by BrdU incorporation. The exposure of cells to the receptor-specific antagonist D-Lys-3-GHRP-6 abolished the proliferative effect of ghrelin. By contrast, ghrelin showed no significant effect on cell differentiation. The expression of GHS-R1a was significantly increased by ghrelin treatment. The analysis of signaling pathways showed that ghrelin caused rapid activation of ERK1/2 and Akt, which were blocked by the GHS-R1a antagonist. In addition, ghrelin stimulated the phosphorylation of Akt downstream effectors, such as glycogen synthase kinase (GSK)-3b, mammalian target of rapamycin (mTOR), and p70 S6K. The activation of STAT3 was also caused by ghrelin treatment. Furthermore, pretreatment of cells with specific inhibitors of MEK/ERK1/2, phosphatidylinositol-3-kinase (PI3K)/Akt, mTOR, and Jak2/STAT3 attenuated ghrelin-induced cell proliferation. Taken together, our results support a role for ghrelin in adult hippocampal neurogenesis and suggest the involvement of the ERK1/2, PI3K/Akt, and STAT3 signaling pathways in the mediation of the actions of ghrelin on neurogenesis. Our data also suggest that PI3K/Akt-mediated inactivation of GSK-3b and activation of mTOR/p70 S6K contribute to the proliferative effect of ghrelin.

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Effects of ghrelin and des-acyl ghrelin on neurogenesis of the rat fetal spinal cord

Cited by 82 publications

References 24 publications

Ontogenetic and tissue-specific expression of preproghrelin in the Atlantic halibut, Hippoglossus hippoglossus L.

Ontogenetic and tissue-specific expression of preproghrelin in the Atlantic halibut, Hippoglossus hippoglossus L.

Ghrelin, des-acyl ghrelin and obestatin: Three pieces of the same puzzle

Multiple signaling pathways mediate ghrelin-induced proliferation of hippocampal neural stem cells

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