The Mycotoxin Ochratoxin A Alters Intestinal Barrier and Absorption Functions but Has No Effect on Chloride Secretion

Maresca, Marc; Mahfoud, Radhia; Pfohl‐Leszkowicz, Annie; Fantini, Jacques

doi:10.1006/taap.2001.9254

Cited by 75 publications

(47 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Real-time PCR data of SGLT-1 expression were consistent with the high activity of SGLT-1 in HT-29-D4 cells (18,19,32) and the very weak expression of this function in Caco-2 cells (18,33,34). However, as the involvement of NPC1L1 in intestinal cholesterol absorption is a recent discovery (21), it is not known yet whether the level of cholesterol absorption is associated with NPC1L1 expression in intestinal cell lines.…”

Section: Cholesterol Uptake Studiessupporting

confidence: 56%

“…Two human epithelial intestinal cell lines previously used for studying intestinal transport functions, HT-29-D4 (18,19,32) and Caco-2 (30,36), were used in this study. These cell lines were characterized with respect to the expression of cholesterol transporters, especially NPC1L1, which is required for intestinal uptake of both cholesterol and phytosterols and plays a major role in cholesterol homeostasis (20,21).…”

Section: Discussionmentioning

confidence: 99%

“…Cholesterol transport studies were conducted with Caco-2 and HT-29-D4 human intestinal cell lines (17). Although widely used as in vitro models for the intestinal epithelium, such cell lines may show significant differences in their transport capacities (18), which may reflect specific biochemical membrane compositions (17). For this reason, we have studied the expression of mRNA coding for two major intestinal transporters: the sodium-dependent apical glucose transporter SGLT-1 (19) and the intestinal phytosterol and cholesterol transporter Niemann-Pick C1 like 1 (NPC1L1) (20).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Interaction of cholesterol with sphingosine

Garmy¹,

Taïeb²,

Yahi³

et al. 2005

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

Molecular associations between sphingomyelin and cholesterol provide a molecular basis for the colocalization of these lipids in plasma membrane microdomains (lipid rafts) and for the inhibitory effect of sphingomyelin on the intestinal absorption of cholesterol. Using surface pressure measurements at the air-water interface, we showed that sphingosine, the common sphingoid backbone of most sphingolipids, formed condensed lipid complexes with cholesterol. Structure-activity relationship studies with long-chain analogs of sphingosine, together with molecular mechanics simulations, were consistent with a specific interaction between sphingosine and the ␣ face of cholesterol. The uptake of micellar cholesterol and the effect of sphingosine on cholesterol absorption were studied with two human model intestinal epithelial cell lines, Caco-2 and HT-29-D4. Realtime PCR quantifications of the putative cholesterol transporter Niemann-Pick C1 like 1 (NPC1L1) mRNA revealed that, in these cell lines, the activity of cholesterol transport correlated with the level of NPC1L1 expression. In both cell lines, sphingosine induced a dose-dependent decrease of cholesterol absorption. Yet the effect of sphingosine was more dramatic in Caco-2 cells, which also displayed the highest expression of NPC1L1 mRNA. Altogether, these data suggested that sphingosine interacts specifically with cholesterol and inhibits the intestinal NPC1L1-dependent transport of micellar cholesterol. It has been known for several years that cholesterol interacts with sphingomyelin (1-3) and that this interaction is of high biological significance for two main reasons. i ) The formation of ordered lipid domains in the plasma membrane of eukaryotic cells is, at least in part, driven by lipid-lipid interactions (4, 5). Among them, the molecular association between sphingomyelin and cholesterol is an important parameter that controls the segregation of both lipids into cholesterol-enriched microdomains usually referred to as lipid rafts (6). These microdomains of the plasma membrane are involved in key cellular functions, such as the control of signal transduction pathways, and they are used as landing platforms and ports of entry by many pathogens or toxins (7)(8)(9). ii ) On the other hand, the formation of cholesterol-sphingomyelin molecular complexes in the intestinal lumen explains the mutual inhibitory effects of cholesterol and sphingomyelin on their intestinal absorption (10). Indeed, it was recently demonstrated that sphingomyelin decreased the absorption of cholesterol by affecting the thermodynamic activity (i.e., the active concentration) of cholesterol monomers in the small intestine (11). The process of intestinal sphingomyelin absorption is complex. A part of sphingomyelin can be directly absorbed by the intestinal epithelium, but this phosphorylated sphingolipid is also cleaved by intestinal sphingomyelinases, giving rise to ceramide and phosphorylcholine (12, 13). Ceramide is poorly absorbed and is further hydrolyzed into fatty acid and ...

show abstract

Section: Cholesterol Uptake Studiessupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Interaction of cholesterol with sphingosine

Garmy¹,

Taïeb²,

Yahi³

et al. 2005

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, it is important to note that the dose administered by Galtier et al (1979) was 50 times higher than the dose administered by Hagelberg et al (1989). It is well known that OTA can alter barrier and absorption functions of the intestinal epithelium, and even potentiate its own absorption through paracellular pathways (Maresca et al, 2001;Subramanian et al, 1991). Moreover, Suzuki et al (1977) observed catarrhal enteritis produced by OTA or OTα through small intestine after a single oral dose of 15 mg/kg b.w.…”

Section: Absorptionmentioning

confidence: 99%

Ochratoxin A kinetics: A review of analytical methods and studies in rat model

Vettorazzi

González-Peñas

Ceráin

2014

Food and Chemical Toxicology

View full text Add to dashboard Cite

Ochratoxin A (OTA) is a thermostable mycotoxin that contaminates a great variety of foodstuffs. It is nephrotoxic in all of the mammalian species tested, being the pig the most sensitive one; among rodents, rats are the most susceptible to OTA carcinogenicity. Kinetics, by studying the absorption, distribution, metabolism and excretion of xenobiotics, is an important tool for the extrapolation of animal toxicity data. The most important kinetic studies performed with OTA in rats have been reviewed, together with the different methods used for OTA quantification in biological matrices. Thirteen studies in Wistar, Sprague-Dawley or F344 rats, using radiolabeled OTA or TLC, HPLC-FLD or HPLC-MS have been summarized. Very often methods validated for food have been directly applied to tissues. Strain, sex and age differences have been detected but the interpretation is difficult due to the different experimental conditions, and the connection of the several factors that may account for these differences.

show abstract

“…The mechanisms involved in the disturbances of the TEER caused by mycotoxins could be a result of a decrease of two specific isoforms of the claudin protein from the tight junctions [10,11]. Also, effects on the protein content of plasma membrane microdomains, which are known to regulate the tight junction assembly and intestinal transport activity [12] and a loss of cell-matrix interactions [13] may explain the effects of mycotoxins on TEER. In order to maintain an effective barrier function, epithelia need to exist in a constant state of regeneration.…”

mentioning

confidence: 99%

The Gut Immune Parameters for Mycotoxin Research

Wan¹

2014

J Biomol Res Ther

View full text Add to dashboard Cite

The Mycotoxin Ochratoxin A Alters Intestinal Barrier and Absorption Functions but Has No Effect on Chloride Secretion

Cited by 75 publications

References 45 publications

Interaction of cholesterol with sphingosine

Interaction of cholesterol with sphingosine

Ochratoxin A kinetics: A review of analytical methods and studies in rat model

The Gut Immune Parameters for Mycotoxin Research

Contact Info

Product

Resources

About