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Lipid-Based Nanocarriers in Lymphatic Transport of Drugs: Retrospect and Prospects
Published in Bhupinder Singh, Rodney J. Y. Ho, Jagat R. Kanwar, NanoBioMaterials, 2018
Vikas Rana, Sunil Kamboj, Sheshank Sethi
Interestingly, the lipid uptake from intestinal lumen requires several proteins on the apical brush border membrane i.e. N1PC1 (Niemann Pick C1-like), SRB-2 (Scavenger receptor B-1) and CD36. However, two ABC half transporters located on the apical membrane of enterocytes (ABCG5 and ABCG8) are responsible for cholesterol efflux back to the intestinal lumen to limit the cholesterol absorption. Another ABC transporter present at basolateral membrane is ABCA1 that mediates the high-density lipoprotein secretion from the enterocytes (Hui et al., 2008). Table 4.1 summarizes the examples of substrates and inhibitors of various ABC transporters.
Endocrine disrupting toxicity of aryl organophosphate esters and mode of action
Published in Critical Reviews in Environmental Science and Technology, 2023
Wenxin Hu, Peng Gao, Lei Wang, Jianying Hu
LXR-antagonistic activities of TPHP and EHDPP were discovered by an LXR pull-down assay combined with nontarget high-resolution mass spectrometry screening in indoor dust. The potency of TPHP (IC50: 1477 nM for LXRα and 762 nM for LXRβ) was similar to that of the strong LXR positive antagonist SR9238 (IC50: 824.7 nM for LXRα and 446.4 nM for LXRβ), based on a two-hybrid yeast assay (Hu et al., 2019b). The LXR transcriptional activity after TPHP exposure was demonstrated by the downregulated expression of ABCA1 and ABCG1, and lysophosphatidylcholine acyltransferase 3 (Lpcat3), these genes are the downstream target genes of LXRs in macrophages (Hu et al., 2019b, 2020). Because ABCA1 and ABCG1 play critical roles in the efflux of excess cellular cholesterol in macrophages, their selective inactivation could cause an imbalance between the uptake and ABCA1- and ABCG1-mediated efflux of cholesterol, thus leading to the formation of foam cells. The effects of TPHP on cholesterol efflux and foam cell formation were also observed in RAW26.4 cells and peritoneal macrophages (Hu et al., 2019b). In an atherosclerotic mouse model (ApoE−/−), TPHP exposure at a concentration of 10 mg/kg for 3 months enlarged the area of atherosclerotic lesions in the en-face stained aorta and aortic roots by promoting foam cell formation, demonstrating that TPHP exposure induced AS via LXR pathway.
Hyperlipidemia and male infertility
Published in Egyptian Journal of Basic and Applied Sciences, 2021
Zainab Bubakr Hamad Zubi, Hamad Abdulsalam Hamad Alfarisi
Fatty acids metabolism has an important function in sperm structure and male reproduction. Impairment of this metabolism affects spermatogenesis. The testes have an active lipid metabolism that maintain the rearrangement of fatty acids during spermatogenesis. In double LXR knockout mice, the level of mRNA of sterol response element binding protein-1 c (srebp1c) and fatty acid synthase (fas) were found to be decreased [77]. Expression of LXRβ receptors is universal throughout the epididymis; whereas, LXRα receptors are expressed slightly less in the cauda than in the caput of the epididymis in wild type mice (Frenoux et al., 2004)[8]. Neutral lipid accumulation in the smooth muscle cells and apical epithelial cells of the epididymis observed in LXRα; β−/−. Cholesterol ester accumulation is most probably a subsequent to the loss of ATP-binding transporters A1 (ABCA1) involved in cholesterol efflux [78]. Loss of LXRβ modifies the genes involved in fatty acid metabolism in the caput of the epididymis. Stearoyl Co-A desaturases 1 and 2 (scd1 and scd2) and srebp1c are reduced in LXRα; β−/− and LXRβ−/− mice. These genes encode enzymes responsible for the desaturation of fatty acids mainly palmitic and stearic acid to produce palmitoleic and oleic acids involved in the production of triglycerides, or incorporated in the cholesteryl esters [73]. Sperm analysis of LXR knockout mice demonstrated that a significant reduction in the sperm count was observed in LXRβ−/− mice; whereas, sperm viability was reduced in both LXRβ−/− and LXRα−/− [74]. Liver X receptors knockout (LXRα; β−/−) mice showed a severe reduction in sperm count associated with structural abnormalities. In addition they exhibited structural fragility and abnormal flagella with various degrees of angulation (Frenoux et al., 2004)[8].