IGF regulation of neutral amino acid transport in the BeWo choriocarcinoma cell line (b30 clone): Evidence for MAP kinase-dependent and MAP kinase-independent mechanisms

Fang, Junguo; Mao, Dailing; Smith, Carl H.; Fant, Michael E.

doi:10.1016/j.ghir.2006.08.002

Cited by 24 publications

(22 citation statements)

References 31 publications

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“…The apical microvillous membrane of the syncytiotrophoblast expresses numerous hormone receptors, such as insulin [42,43], IGF-I [44], and leptin [45] receptors, consistent with regulation of placental function by maternal hormones. It has been shown that insulin [46][47][48][49], IGF-I [48,50], leptin [51], and cytokines such as interleukin 6 (IL-6) [52] and tumor necrosis factor alpha [52] are positive regulators of system A amino acid transporters. Moreover, the activation of trophoblast system A activity by IL-6, leptin, and oleic acid appears to involve the transcription factor STAT-3 [49,52,53], indicating that there are common pathways to integrate and ''sense'' different maternal metabolic cues.…”

Section: Placental Function and Maternal-fetal Resource Allocationmentioning

confidence: 99%

The Role of Placental Nutrient Sensing in Maternal-Fetal Resource Allocation1

Díaz

Powell

Jansson

2014

Biology of Reproduction

121

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The placenta mediates maternal-fetal exchange and has historically been regarded as a passive conduit for nutrients. However, emerging evidence suggests that the placenta actively responds to nutritional and metabolic signals from the mother and the fetus. We propose that the placenta integrates a multitude of maternal and fetal nutritional cues with information from intrinsic nutrient-sensing signaling pathways to match fetal demand with maternal supply by regulating maternal physiolo-

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Section: Placental Function and Maternal-fetal Resource Allocationmentioning

confidence: 99%

The Role of Placental Nutrient Sensing in Maternal-Fetal Resource Allocation1

Díaz

Powell

Jansson

2014

Biology of Reproduction

121

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“…In contrast, IGF-I did not affect the surface area of the placenta, but appeared to divert nutrients from mother to fetus. Further evidence supporting the role of IGFs in mediating nutrient transfer comes from in vitro studies, where in both cultured human primary trophoblast cells and in the BeWo choriocarcinoma cell line, physiological levels of IGF-I enhance amino acid uptake [31, 32]. …”

Section: The Igf Axis In the Placentamentioning

confidence: 99%

“…Since the mTOR pathway is important in mediating both nutrient and growth factor signals to promote cellular growth, it is likely that mTOR is also involved in regulating normal placental development. A recent study by Wen et al [66] demonstrating that mTOR acts as a nutrient sensor to promote proliferation of immortalized human trophoblast cells supports this hypothesis; however, another group using the choriocarcinoma cell line BeWo have reported that the ability of IGF to regulate amino acid transport does not require mTOR [32]. It would therefore be interesting to see if mTOR is involved in IGF-mediated trophoblast events in primary placental cells or in explant cultures.…”

Section: Igf1r Signalling Events In the Placentamentioning

confidence: 99%

The IGF Axis and Placental Function

Forbes

Westwood²

2008

Horm Res Paediatr

126

125

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It is well known that the insulin-like growth factor (IGF) axis is an important regulator of foetal growth and in recent years, it has been suggested that the ligands IGF-I and IGF-II may, in part, mediate this effect by promoting proper placental development and function. In other tissues, IGF effects on metabolism, proliferation and differentiation are primarily mediated via IGF binding protein-regulated interaction of IGFs with the type 1 IGF receptor and therefore here, we review the placental expression and postulated role, of each of the IGF axis components and discuss the cellular mechanisms through which these effects are exerted.

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“…The current evidence shows that SNAT2 gene expression is activated by PKA via cAMP and also by PKC, via MAPK, or even by certain hormones such as estradiol (11,15,23). These data suggest that the promoter region of the SNAT2 gene has a complex regulatory mechanism that is largely unknown.…”

mentioning

confidence: 82%

Promoter characterization and role of CRE in the basal transcription of the rat SNAT2 gene

Ortíz

Alemán

Escamilla-Del-Arenal

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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Small neutral amino acid transporter 2 (SNAT2) is the most abundant and ubiquitous transporter for zwitterionic short-chain amino acids. The activity of this amino acid transporter is stimulated in vivo or in vitro by glucagon or cAMP analogs. However, it is not known whether the increase in activity at the protein level is due to an increase in SNAT2 gene transcription. Thus, the aim of the present work was to study whether cAMP was able to stimulate SNAT2 gene expression and to localize and characterize the presence of cAMP response elements (CRE) in the promoter that controls the expression of the rat SNAT2 gene. We found that consumption of a high-protein diet that increased serum glucagon concentration or the administration of glucagon or incubation of hepatocytes with forskolin increased the SNAT2 mRNA level. We then isolated the 5= regulatory region of the SNAT2 gene and determined that the transcriptional start site was located 970 bp upstream of the translation start codon. We identified two potential CRE sites located at Ϫ354 and Ϫ48 bp. Our results, using deletion analysis of the 5= regulatory region of the SNAT2 gene, revealed that the CRE site located at Ϫ48 bp was fully responsible for SNAT2 regulation by cAMP. This evidence was strongly supported by mutation of the CRE site and EMSA and ChIP analysis. Alignment of rat, mouse, and human sequences revealed that this CRE site is highly conserved among species, indicating its essential role in the regulation of SNAT2 gene expression.

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IGF regulation of neutral amino acid transport in the BeWo choriocarcinoma cell line (b30 clone): Evidence for MAP kinase-dependent and MAP kinase-independent mechanisms

Cited by 24 publications

References 31 publications

The Role of Placental Nutrient Sensing in Maternal-Fetal Resource Allocation1

The Role of Placental Nutrient Sensing in Maternal-Fetal Resource Allocation1

The IGF Axis and Placental Function

Promoter characterization and role of CRE in the basal transcription of the rat SNAT2 gene

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