Cyclosporine A Reduces ATP-Binding Cassette Transporter G5 (ABCG5) and G8 (ABCG8) Gene Expression and Protein in Caco-2 Cells

Ito, Matthew K.; Ganesan, Shobana; Judd, Grace I.; Zargar, Atanaz; Olyaie, Ali J.

doi:10.1016/j.jacl.2012.04.073

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“…Adenosine triphosphate (ATP)-binding cassette transporters combined with transporter G superfamily member 8 antibodies (ABCG8) then return unabsorbed cholesterol to the lumen of the intestine for excretion (Chen et al, 2011). Caco-2 cell monolayers have routinely been used as an in vitro model to mimic substance absorption by the human intestinal epithelium (Picariello et al, 2013): NPC1L1 (Alrefai et al, 2007), ABCG8 (Ito et al, 2012), SREBP-2 (Field et al, 2001), ACAT2 (Song et al, 2006), and MTP (Mathur et al, 1997) are all expressed in the Caco-2 cell model. Nagaoka et al (1997) reported that the suppression of cholesterol intestinal epithelia absorption by Caco-2 cell studies is part of the mechanism for the hypocholesterolemic action.…”

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confidence: 99%

Novel milk casein–derived peptides decrease cholesterol micellar solubility and cholesterol intestinal absorption in Caco-2 cells

Jiang

Pan

Zhang

et al. 2020

Journal of Dairy Science

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This study sought to assess the cholesterol-lowering activity of peptides obtained from milk casein hydrolyzed with neutrase. The bioactive peptides were separated using a Sephadex G-10 chromatographic column (Amersham Pharmacia Biotech, Uppsala, Sweden) after ultrafiltration using a 1-kDa molecular mass cutoff membrane. Via ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry, we determined that peptides Thr- (185)(186)(187)(188)(189)(190)] reduced micellar cholesterol solubility. After Caco-2 cells were treated with LQPE, VLPVPQ, and VAPFPE, the Niemann-Pick C1-Like 1 (NPC1L1) protein levels decreased by (means ± SEM) 19.33 ± 2.47%, 52.1 ± 3.77%, and 23.09 ± 8.52%, respectively, compared with the control group. Treatment with each peptide induced significant upregulation of ATP binding cassette subfamily G member 8 antibody (ABCG8) mRNA expression by 398.1 ± 23.27%, 86.4 ± 27.07%, and 92.8 ± 8.49%. We found that VLPVPQ and LQPE significantly upregulated ATP-binding cassette transporter A1 (ABCA1) transcription by 203.9 ± 8.44% and 220.8 ± 36.42% respectively, whereas VLPVPQ significantly decreased mRNA expression of acetyl-CoA-acetyltransferase 2 (ACAT2) and microsomal triacylglycerols (MTP). The cholesterol-lowering action of milk-derived peptides may be induced by suppression of micellar cholesterol solubility and affects the expression of cholesterol absorption-related proteins and enzymes in intestinal epithelial cells. This research discovers new milk-derived peptides with decreasing cholesterol micellar solubility and provides a theoretical basis of in vitro cholesterollowering effects of peptides.

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