New Insights into Orphan Nuclear Receptor SHP in Liver Cancer

Zou, An; Lehn, Sarah; Magee, Nancy; Zhang, Yuxia

doi:10.11131/2015/101162

Cited by 25 publications

(12 citation statements)

References 70 publications

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“…Over-expression of SHP causes dysregulation of lipid metabolism through indirect activation of PPARγ and SREBP-1c, and inhibition of HNF4α signaling [38, 49]. Shp also inhibits many other receptors involved in lipid metabolism (HNF4α, LXR, PXR) [38, 49, 50]. GVAD-HFD and LF12-LF12 protocols, which stimulated the stellate and inflammatory clusters, appreciably decreased Shp expression (Table 3).…”

Section: Discussionmentioning

confidence: 99%

Diet-dependent retinoid effects on liver gene expression include stellate and inflammation markers and parallel effects of the nuclear repressor Shp

Maguire

Bushkofsky

Larsen

et al. 2017

The Journal of Nutritional Biochemistry

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For mice, a maternal vitamin A (VA) deficient diet initiated from mid-gestation (GVAD) produces serum retinol deficiency in mature offspring. We hypothesize that the effects of GVAD arise from pre-weaning developmental changes. We compare the effect of this GVAD protocol in combination with a post-weaning high fat diet (HFD) or high carbohydrate diet (LF12). Each is compared to an equivalent VA sufficient combination. GVAD extensively decreased serum retinol and liver retinol, retinyl esters, and retinoid homeostasis genes (Lrat, Cyp26b1, and Cyp26a1). These suppressions were each more effective with LF12 than with HFD. Post-weaning initiation of VA deficiency with LF12 depleted liver retinoids, but serum retinol was unaffected. Liver retinoid depletion, therefore, precedes serum attenuation. Maternal LF12 decreased the obesity response to the HFD, which was further decreased by GVAD. LF12 fed to the mother and offspring extensively stimulated genes marking stellate activation (Col1a1, Timp2, and Cyp1b1) and novel inflammation markers (Ly6d, Trem2, Nupr1). The GVAD with LF12 diet combination suppressed these responses. GVAD in combination with the HFD increased these same clusters. A further set of expression differences on the HFD when compared to a high carbohydrate diet were prevented when GVAD was combined with HFD. Most of these GVAD gene changes match published effects from deletion of Nr0b2/Shp, a retinoid-responsive, nuclear co-repressor that modulates metabolic homeostasis. The stellate and inflammatory increases seen with the high carbohydrate, LF12 diet may represent postprandial responses. They depend on retinol and Shp, but the regulation reverses with a HFD.

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Section: Discussionmentioning

confidence: 99%

Diet-dependent retinoid effects on liver gene expression include stellate and inflammation markers and parallel effects of the nuclear repressor Shp

Maguire

Bushkofsky

Larsen

et al. 2017

The Journal of Nutritional Biochemistry

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“…The degradation of auxin/IAA and the JAZ complex causes activation of auxin-or JA-responsive genes (21). In animals, nuclear receptors, which comprise a large family of transcription factors (25), regulate gene expression, and among them, mall heterodimer partner contains a putative ligand-binding domain but lacks a DNA-binding domain (25,26), regulating gene expression as a co-repressor (27). Although the caryophyllene-TPL pair is only the first case so far, and thus we cannot generalize the current finding for all VOC sensing, it is intriguing that plants appear to have evolved a VOC-sensing mechanism using nuclear proteins rather than membrane receptors such as odorant receptors in animals.…”

Section: Plant Transcriptional Regulators Involved In Voc Responsesmentioning

confidence: 99%

Transcriptional regulators involved in responses to volatile organic compounds in plants

Nagashima

Higaki

Koeduka

et al. 2019

Journal of Biological Chemistry

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Edited by Joseph M. JezField studies have shown that plants growing next to herbivore-infested plants acquire higher resistance to herbivore damage. This increased resistance is partly due to regulation of plant gene expression by volatile organic compounds (VOCs) released by plants that sense environmental challenges such as herbivores. The molecular basis for VOC sensing in plants, however, is poorly understood. Here, we report the identification of TOPLESS-like proteins (TPLs) that have VOC-binding activity and are involved in VOC sensing in tobacco. While screening for volatiles that induce stress-responsive gene expression in tobacco BY-2 cells and tobacco plants, we found that some sesquiterpenes induce the expression of stress-responsive genes. These results provided evidence that plants sense these VOCs and motivated us to analyze the mechanisms underlying volatile sensing using tobacco as a model system. Using a pulldown assay with caryophyllene derivative-linked beads, we identified TPLs as transcriptional co-repressors that bind volatile caryophyllene analogs. Overexpression of TPLs in cultured BY-2 cells or tobacco leaves reduced caryophyllene-induced gene expression, indicating that TPLs are involved in the responses to caryophyllene analogs in tobacco. We propose that unlike animals, which use membrane receptors for sensing odorants, a transcriptional co-repressor plays a role in sensing and mediating VOC signals in plant cells.For terrestrial animals, odorants or volatile organic compounds (VOCs) 5 possess important biological and ecological information such as food, predator, and species. Sensing these chemical cues, animals take appropriate behavior such as attraction or avoidance, ensuring their survival. Plants also have to acquire information from the external environment and take appropriate action for survival. Defense or stress-related genes are up-regulated upon exposure to specific VOCs to prepare for environmental change in plants (1-4). For example, defense genes are induced in healthy lima bean leaves upon exposure to VOCs from infested leaves, but not from healthy or artificially wounded leaves (5). In addition, VOCs released from infested leaves prime neighboring plants for direct and indirect defense against future herbivore attack (6). VOCs are also used as cues for host selection and location by parasitic plants (7). Several individual compounds from host plants also show attractiveness to parasitic plants. Regardless of accumulated evidence for the VOC effects in plants, a molecular basis for the VOC detection by plant cells has not been revealed.In animals, VOCs are recognized by odorant receptors in the olfactory neural system that constitutes the largest G protein-coupled receptor (GPCR) family. In contrast, plants have only a few GPCR genes that appear to have different functions (8). It has been unclear how VOCs are sensed and the information is converted to signals that induce the specific responses in plant cells at the level of receptors. It is possible that plants have a...

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“…SHP is thus involved in bile acid, cholesterol, triglyceride, glucose, and drug metabolism. SHP mainly plays important role in the negative regulation of the conversion of cholesterol to bile acids via FXR, as well in regulating the expression of genes playing roles in bile acid transport (BSEP, NTCP), lipid metabolism (SREBP1C), and gluconeogenesis (PEPCK, G6Pase) (Zhang et al, 2011; Zou et al, 2015). …”

Section: Competition For Coactivators and Cross-talk In Pxr-mediated mentioning

confidence: 99%

Pregnane X Receptor (PXR)-Mediated Gene Repression and Cross-Talk of PXR with Other Nuclear Receptors via Coactivator Interactions

2016

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Pregnane X receptor is a ligand-activated nuclear receptor (NR) that mainly controls inducible expression of xenobiotics handling genes including biotransformation enzymes and drug transporters. Nowadays it is clear that PXR is also involved in regulation of intermediate metabolism through trans-activation and trans-repression of genes controlling glucose, lipid, cholesterol, bile acid, and bilirubin homeostasis. In these processes PXR cross-talks with other NRs. Accumulating evidence suggests that the cross-talk is often mediated by competing for common coactivators or by disruption of coactivation and activity of other transcription factors by the ligand-activated PXR. In this respect mainly PXR-CAR and PXR-HNF4α interference have been reported and several cytochrome P450 enzymes (such as CYP7A1 and CYP8B1), phase II enzymes (SULT1E1, Gsta2, Ugt1a1), drug and endobiotic transporters (OCT1, Mrp2, Mrp3, Oatp1a, and Oatp4) as well as intermediate metabolism enzymes (PEPCK1 and G6Pase) have been shown as down-regulated genes after PXR activation. In this review, I summarize our current knowledge of PXR-mediated repression and coactivation interference in PXR-controlled gene expression regulation.

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New Insights into Orphan Nuclear Receptor SHP in Liver Cancer

Cited by 25 publications

References 70 publications

Diet-dependent retinoid effects on liver gene expression include stellate and inflammation markers and parallel effects of the nuclear repressor Shp

Diet-dependent retinoid effects on liver gene expression include stellate and inflammation markers and parallel effects of the nuclear repressor Shp

Transcriptional regulators involved in responses to volatile organic compounds in plants

Pregnane X Receptor (PXR)-Mediated Gene Repression and Cross-Talk of PXR with Other Nuclear Receptors via Coactivator Interactions

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