Ghrelin induces cell migration through GHS-R, CaMKII, AMPK, and NF-κB signaling pathway in glioma cells

Chen, Jia Hong; Huang, Ssu Ming; Chen, Chun-Chung; Tsai, Cheng Fang; Yeh, Wei Lan; Chou, Shao Jiun; Hsieh, Wen Tsong; Lu, Dah Yuu

doi:10.1002/jcb.23209

Cited by 57 publications

(52 citation statements)

References 77 publications

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“…involved in cell motility (Dixit et al 2006, Chen et al 2011. In our study, we observed GHR and GRLN-R1a immunolabelling in astrocytes of the hypothalamic arcuate nucleus and of the dentate gyrus in the hippocampus.…”

Section: Discussionsupporting

confidence: 65%

Differential effects of GH and GH-releasing peptide-6 on astrocytes

Baquedano¹,

Chowen²,

Argente³

et al. 2013

Journal of Endocrinology

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GH and GH secretagogues (GHSs) are involved in many cellular activities such as stimulation of mitosis, proliferation and differentiation. As astrocytes are involved in developmental and protective functions, our aim was to analyse the effects of GH and GH-releasing hexapeptide on astrocyte proliferation and differentiation in the hypothalamus and hippocampus. Treatment of adult male Wistar rats with GH (i.v., 100 mg/day) for 1 week increased the levels of glial fibrillary acidic protein (GFAP) and decreased the levels of vimentin in the hypothalamus and hippocampus. These changes were not accompanied by increased proliferation. By contrast, GH-releasing hexapeptide (i.v., 150 mg/day) did not affect GFAP levels but increased proliferation in the areas studied. To further study the intracellular mechanisms involved in these effects, we treated C6 astrocytoma cells with GH or GH-releasing hexapeptide and the phosphatidylinositol 3 0 -kinase (PI3K) inhibitor, LY294002, and observed that the presence of this inhibitor reverted the increase in GFAP levels induced by GH and the proliferation induced by GH-releasing hexapeptide. We conclude that although GH-releasing hexapeptide is a GHS, it may exert GH-independent effects centrally on astrocytes when administered i.v., although the effects of both substances appear to be mediated by the PI3K/Akt pathway.

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Section: Discussionsupporting

confidence: 65%

Differential effects of GH and GH-releasing peptide-6 on astrocytes

Baquedano¹,

Chowen²,

Argente³

et al. 2013

Journal of Endocrinology

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“…2010) and CaMKII activation in glial cells (Chen et al. 2011). To our knowledge, we are the first to report AG‐induced phosphorylation of CaMKII in skeletal muscle.…”

Section: Discussionmentioning

confidence: 99%

Acylated and unacylated ghrelin do not directly stimulate glucose transport in isolated rodent skeletal muscle

Cervone

Dyck

2017

Physiol Rep

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Emerging evidence implicates ghrelin, a gut‐derived, orexigenic hormone, as a potential mediator of insulin‐responsive peripheral tissue metabolism. However, in vitro and in vivo studies assessing ghrelin's direct influence on metabolism have been controversial, particularly due to confounding factors such as the secondary rise in growth hormone (GH) after ghrelin injection. Skeletal muscle is important in the insulin‐stimulated clearance of glucose, and ghrelin's exponential rise prior to a meal could potentially facilitate this. This study was aimed at elucidating any direct stimulatory action that ghrelin may have on glucose transport and insulin signaling in isolated rat skeletal muscle, in the absence of confounding secondary factors. Oxidative soleus and glycolytic extensor digitorum longus skeletal muscles were isolated from male Sprague Dawley rats in the fed state and incubated with various concentrations of acylated and unacylated ghrelin in the presence or absence of insulin. Ghrelin did not stimulate glucose transport in either muscle type, with or without insulin. Moreover, GH had no acute, direct stimulatory effect on either basal or insulin‐stimulated muscle glucose transport. In agreement with the lack of observed effect on glucose transport, ghrelin and GH also had no stimulatory effect on Ser473 AKT or Thr172 AMPK phosphorylation, two key signaling proteins involved in glucose transport. Furthermore, to our knowledge, we are among the first to show that ghrelin can act independent of its receptor and cause an increase in calmodulin‐dependent protein kinase 2 (CaMKII) phosphorylation in glycolytic muscle, although this was not associated with an increase in glucose transport. We conclude that both acylated and unacylated ghrelin have no direct, acute influence on skeletal muscle glucose transport. Furthermore, the immediate rise in GH in response to ghrelin also does not appear to directly stimulate glucose transport in muscle.

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“…The ghrelin receptor is also present in astrocytomas, with astrocytoma cell lines expressing higher levels of GHSR1a compared with primary cultures of normal astrocytes [92,93]. Ghrelin promotes cell motility in astrocytomas and, given that it is a positive regulator of the somatotropic axis, it could play a role in astrocytoma cell growth and function with an endogenous hormonal loop, critical in astrocytoma motility and invasiveness, possibly being involved [93].…”

Section: Ghrelin Receptors In Astrocytesmentioning

confidence: 99%

Involvement of Astrocytes in Mediating the Central Effects of Ghrelin

Frago

Chowen

2017

IJMS

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Although astrocytes are the most abundant cells in the mammalian brain, much remains to be learned about their molecular and functional features. Astrocytes express receptors for numerous hormones and metabolic factors, including the appetite-promoting hormone ghrelin. The metabolic effects of ghrelin are largely opposite to those of leptin, as it stimulates food intake and decreases energy expenditure. Ghrelin is also involved in glucose-sensing and glucose homeostasis. The widespread expression of the ghrelin receptor in the central nervous system suggests that this hormone is not only involved in metabolism, but also in other essential functions in the brain. In fact, ghrelin has been shown to promote cell survival and neuroprotection, with some studies exploring the use of ghrelin as a therapeutic agent against metabolic and neurodegenerative diseases. In this review, we highlight the possible role of glial cells as mediators of ghrelin’s actions within the brain.

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Ghrelin induces cell migration through GHS-R, CaMKII, AMPK, and NF-κB signaling pathway in glioma cells

Cited by 57 publications

References 77 publications

Differential effects of GH and GH-releasing peptide-6 on astrocytes

Differential effects of GH and GH-releasing peptide-6 on astrocytes

Acylated and unacylated ghrelin do not directly stimulate glucose transport in isolated rodent skeletal muscle

Involvement of Astrocytes in Mediating the Central Effects of Ghrelin

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