Effect of bile acids on the expression of MRP3 and MRP4: An In vitro study in HepG2 cell line

Pérez-Pineda, Suilma Ivette; Baylón-Pacheco, Lidia; Espíritu-Gordillo, Patricia; Tsutsumi, Vı́ctor; Rosales‐Encina, José Luis

doi:10.1016/j.aohep.2021.100325

Cited by 14 publications

(7 citation statements)

References 29 publications

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“…In patients with HCC, the BSEP level is also decreased, which is associated with a poor prognosis of the course of the disease [ 145 , 146 ]. Of the basolateral efflux transporters MRP3, MRP4, and MRP6, MRP4 was not detected in HepG2 cells [ 12 , 147 ], and MRP3 and MRP6 titers were 4–20 times lower in HepG2 cells than in hepatocytes.…”

Section: Comparison Of Hepg2 Normal Hepatocyte Hb and Hccmentioning

confidence: 99%

The Curious Case of the HepG2 Cell Line: 40 Years of Expertise

Arzumanian

Kiseleva

Poverennaya

2021

IJMS

175

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Liver cancer is the third leading cause of cancer death worldwide. Representing such a dramatic impact on our lives, liver cancer is a significant public health concern. Sustainable and reliable methods for preventing and treating liver cancer require fundamental research on its molecular mechanisms. Cell lines are treated as in vitro equivalents of tumor tissues, making them a must-have for basic research on the nature of cancer. According to recent discoveries, certified cell lines retain most genetic properties of the original tumor and mimic its microenvironment. On the other hand, modern technologies allowing the deepest level of detail in omics landscapes have shown significant differences even between samples of the same cell line due to cross- and mycoplasma infection. This and other observations suggest that, in some cases, cell cultures are not suitable as cancer models, with limited predictive value for the effectiveness of new treatments. HepG2 is a popular hepatic cell line. It is used in a wide range of studies, from the oncogenesis to the cytotoxicity of substances on the liver. In this regard, we set out to collect up-to-date information on the HepG2 cell line to assess whether the level of heterogeneity of the cell line allows in vitro biomedical studies as a model with guaranteed production and quality.

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Section: Comparison Of Hepg2 Normal Hepatocyte Hb and Hccmentioning

confidence: 99%

The Curious Case of the HepG2 Cell Line: 40 Years of Expertise

Arzumanian

Kiseleva

Poverennaya

2021

IJMS

175

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“…MRP3 (ABCC3) is a member of the ABCC subfamily and is expressed in the liver and intestine of pigs (Figure 7), and the colonization of pig microbiota significantly stimulated MRP3 gene expression in the ileum, cecum, and colon. The expression of another transporter of this subfamily, MRP4 (ABCC4) (Perez-Pineda et al, 2021), was also significantly increased in the ileum after the colonization of pig microbiota, suggesting that the gut microbiota could stimulate BA accumulation in the bowel lumen through transferring BAs in and out of the ileal cells via the ATP-binding cassette (ABC) transporters. The sodium-glucose co-transporter (SGLT1) is one of the nutrient transporters responsible for a portion of the intestinal absorption capacity of water (Thomson et al, 2001) and glucose (Du et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Importance of gut microbiota for bile acid composition and concentration in pigs

Sun¹,

Li²,

Zhou³

et al. 2022

Front. Anim. Sci.

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Several studies on the role of HCA species in regulating glucose homeostasis have indicated their therapeutic value in human obesity and diabetes. There is a clear difference in the percentage of hyocholic acid (HCA) and its derivatives (also known as HCA species) in the total bile acid (BA) pool in the plasma between humans, rats and pigs. However, the role of gut microbiota in BA profiles of pigs remains unclear. We generated five germ-free pig models and six gnotobiotic pig models by fecal microbiota transplantation (FMT). A total of 46 BAs were detected in the jejunum, cecum, colon, and rectum chyme, 37 and 33 BAs were detected in bile, 33 BAs were detected in ileal chyme and liver, and 31 BAs were detected in serum. FMT increased the percentages of HCA species in total bile acids in the serum (79%), liver (78%), and bile (71%), but decreased the proportions of HCA species in the total BAs of the ileum (61%), cecum (47%), colon (51%), and rectum (57%) of pigs, as compared to GF piglets. FMT significantly induced the production of conjugated bile acids in the small intestine and increased the concentrations of free BAs in the large intestine of pigs (P < 0.01). FMT piglets had over 68-fold and 104-fold increases in conjugated BAs in the ileum compared to the germ-free piglets. FMT piglets had an expression pattern distinct from that of germ-free piglets for genes involved in bile acid receptors, synthesis, signaling, and transport. The gene expression levels of the rate-limiting enzyme CYP7A1 and the enzymes CH25H and BAAT involved in BA synthesis were significantly decreased in the liver of FMT piglets, and there was a significant reduction in the gene expression of FXR and TGR5 through the FGFR4/β-Klotho pathway that promotes the BA pool in the liver of piglets after FMT.

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“…The cytotoxicity of deoxycholic acid (DC), chenodeoxycholic acid (CDCA), glycochenodeoxycholic acid (GCDCA), and LCA on Hep G2 cells was evaluated. DC, CDCA, and GCDCA at 750 μM were found to lyse Hep G2 cells after 4 h of incubation [ 41 ]. As shown in Figure 7 , the relative cell viability of Hep G2 and HeLa cells treated with Me-LCA at >750 μM was higher than that of Hep G2 cells treated with DC, CDCA, and GCDCA at 750 μM.…”

Section: Discussionmentioning

confidence: 99%

“…Evaluation of cytotoxicity suggested that bile acid micelles mainly contributed to cell death by removing phospholipids constituting the plasma membrane. However, LCA did not affect the proliferation of Hep G2 cells [ 41 ]. One possible reason for this is the deprotonation of the carboxy group.…”

Section: Discussionmentioning

confidence: 99%

Possible Role of Bent Structure of Methylated Lithocholic Acid on Artificial and Plasma Membranes

Iwasaki

Endo²,

Nakayama³

et al. 2022

Membranes

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Bile acids form micelles that are essential for the absorption of dietary lipids. However, excessive bile acid micelles can disrupt the plasma membrane by removing phospholipids, resulting in cell death. We hypothesized that the bent geometrical structure of the steroid scaffold of bile acids decreases the lipid order (similar to unsaturated phospholipids with cis double bonds), disrupting the plasma membrane. Here, lithocholic acid (LCA), a bile acid, was methylated to prevent micellization. Methylated lithocholic acid (Me-LCA) was mixed with a thin phase-separated lipid bilayer comprising 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and cholesterol (Chol). Me-LCA was not localized in the DPPC-rich rigid phase but localized in the DOPC-rich fluid phase, and excess Me-LCA did not affect the phase separation. Me-LCA is distributed in the plasma and organelle membranes. However, Me-LCA with bent structure did not affect the membrane properties, membrane fluidity, and hydrophobicity of liposomes composed of DOPC, DPPC, and Chol and also did not affect the proliferation of cells.

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Effect of bile acids on the expression of MRP3 and MRP4: An In vitro study in HepG2 cell line

Cited by 14 publications

References 29 publications

The Curious Case of the HepG2 Cell Line: 40 Years of Expertise

The Curious Case of the HepG2 Cell Line: 40 Years of Expertise

Importance of gut microbiota for bile acid composition and concentration in pigs

Possible Role of Bent Structure of Methylated Lithocholic Acid on Artificial and Plasma Membranes

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