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Supplementary and Medicinal Properties of Ulvan Polysaccharides
Published in Shakeel Ahmed, Aisverya Soundararajan, Marine Polysaccharides, 2018
S. Vijayanand, Ashwini Ravi, S. Aisverya, P. N. Sudhaand, J. Hemapriya
Hyperlipidemia is a metabolic condition caused by an increase in lipids, serum triglycerides, total cholesterol and low-density lipoproteins. When untreated, this may lead to several cardiac ailments. Several drugs are available for treating hyperlipidemia, but the reports of undesirable side effects due to the use of the synthetic chemical drugs made it necessary to produce drugs of natural origin [80]. Sulphated polysaccharides from marine organisms are gaining importance due to their distinct biological activities and ulvans are one among the polysaccharides of marine origin. The ulvan polysaccharide has been studied for its hyperlipidemic activities and found to act as a potent antihyperlipidemic agent. Pengzhan et al. (2003) found that ulvan isolated from U. pertusa can efficiently decrease the plasma cholesterol, low-density lipoprotein and triglycerides in ICR rats. It was also found to increase the serum high-density lipoprotein when compared to the control group. A similar phenomenon was observed by Matloub et al. (2013) in hyperlipidemic rats treated with the ulvan polysaccharide isolated from U. fasciata and E. prolifera. It was found that low-molecular-weight ulvan does not reduce the serum cholesterol level, whereas it normalises and raises the high-density lipoprotein levels in serum [81]. Despite its molecular weight, sulphation plays a major role in its activity. Highly sulphated ulvan and acetylated ulvan were found to show better antihyperlipidemic activity and found to decrease low-density lipoprotein levels markedly [82–84]. In a study by Qi and Sheng (2015), the ulvan-treated hyperlipidemic mice were found to up-regulate the bile acid receptor gene of farnesoid X receptor (FXR) and insulin-like receptor of peroxisome proliferator-activated receptor gamma (PPARy) mRNAs, whereas they were found to down-regulate liver X receptor (LXR) mRNA, thereby decreasing hyperlipidemia.
Xenobiotic metabolism and transport in Caenorhabditis elegans
Published in Journal of Toxicology and Environmental Health, Part B, 2021
Jessica H. Hartman, Samuel J. Widmayer, Christina M. Bergemann, Dillon E. King, Katherine S. Morton, Riccardo F. Romersi, Laura E. Jameson, Maxwell C. K. Leung, Erik C. Andersen, Stefan Taubert, Joel N. Meyer
Based upon their overall architecture, NHRs are grouped into the NR1-NR6 classes (Nuclear Receptors Nomenclature, Committee 1999; Weikum, Liu, and Ortlund 2018). The NHRs most prominently involved in detoxification gene regulation belong to the NR1J groups in C. elegans and Drosophila melanogaster and to the NR1I and H classes in mammals. The latter group includes several NHRs with important roles in detoxification such as: the pregnane X receptor (PXR; also known as the steroid and xenobiotic sensing nuclear receptor, SXR, NR1I2); constitutive androstane receptor (CAR, NR1I3); liver X receptor (LXR, NR1H3), farnesoid X receptor (FXR, NR1H4); and vitamin D receptor (VDR, NR1I1) (Hoffmann and Partridge 2015; Mackowiak and Wang 2016; Oladimeji and Chen 2018). However, other NHRs also regulate detoxification genes in various situations, including the peroxisome proliferator-activated receptors (PPARs) and the Hepatocyte Nuclear Factor 4 (HNF4) type NHRs (Wallace and Redinbo 2013). The latter are especially notable as the C. elegans N2 reference genome features a large group of approximately 265 NHRs that appear to have descended and diversified from an HNF4-like ancestor (Taubert, Ward, and Yamamoto 2011). Most of these remain uncharacterized, but recent studies implicated several as putative xenobiotic response regulating NHRs.
Regulation of cytochrome P450 expression by microRNAs and long noncoding RNAs: Epigenetic mechanisms in environmental toxicology and carcinogenesis
Published in Journal of Environmental Science and Health, Part C, 2019
Dongying Li, William H. Tolleson, Dianke Yu, Si Chen, Lei Guo, Wenming Xiao, Weida Tong, Baitang Ning
The pioneering work of Tsuchiya et al.92 first identified and validated miR-27b as a post-transcriptional repressor of CYP1B1. CYP1B1 is responsible for the bioactivation of many procarcinogens and CYP1B1 overexpression and increased enzyme activity have been observed in lung, colon, and breast cancers.118 Stable hybridization between miR-27b and its MRE located in the 3′-UTR of the CYP1B1 mRNA transcript was demonstrated using RNase protection assays and the function of this regulatory mechanism was confirmed using luciferase reporter assays upon miR-27b overexpression or introduction of miR-27b inhibitors; the level of miR-27b was inversely correlated with luciferase activity with reporter gene constructs including the CYP1B1 miR-27-MRE. Gain- and loss-of-function assays have also demonstrated that miR-27b binds to CYP1B1 mRNA and decreases CYP1B1 expression and enzymatic activity.92 miRNAs can also affect CYP expression indirectly by targeting transcriptional activators or repressors of CYP expression (Table 3). For instance, the CYP3A4 gene is regulated by multiple NRs, including PXR, farnesoid X receptor (FXR), and CAR.131,132 Takagi et al.123 have shown that CYP3A4 expression is inhibited at both the mRNA and protein levels upon PXR repression by miR-148. Additionally, miR-34a, miR-30c-1-3p, and miR-27b downregulate CYP3A4 by targeting retinoid X receptor α (RXRα), PXR, and VDR, respectively.108,121,122 When a transcriptional repressor of CYPs is targeted by a miRNA, miRNA-dependent silencing of the repressor will lead to an increase of the CYP level. For example, in CYP2D6-humanized mice, feeding cholic acid leads to a significant decrease of small heterodimer partner (SHP) at the protein level by upregulating miR-142-3p, which targets SHP; miR-142-3p-mediated SHP reduction is accompanied by an increase of CYP2D6 mRNA and protein expression, indicating a potential role of bile acid levels in the transcriptional control of CYP2D6.119Table 3 presents published reports of indirect regulatory pathways by which miRNAs affect the expression of trans-regulatory factors that then regulate CYP genes. It should be noted that additional complexity results from the fact that additional CYP genes are regulated by HNF1A, HNF4A, VDR, and PXR.133,134 Similar miRNA-dependent regulatory pathways involving these CYP genes will require further investigation. Other transcription factors shown to influence the expression of CYP genes, such as the glucocorticoid receptor and FXR, provide additional regulatory targets for miRNA species that could be explored.135,136 miRNAs regulate CYP expression at multiple levels through diverse and novel mechanisms. In the case of CYP2E1, a miRNA species affects transcription by interfering with the assembly of transcription machinery on the promotor region. The multiple mechanisms by which the expression of CYP2E1 is influenced by different miRNAs provides illuminating examples of diverse regulatory systems.