Alterations in the intestine of Patagonian silverside ( Odontesthes hatcheri) exposed to microcystin-LR: Changes in the glycosylation pattern of the intestinal wall and inhibition of multidrug resistance proteins efflux activity

Bieczynski, Flavia; Torres, Walter; Painefilú, Julio C.; Castro, Juan Manuel; Bianchi, Virginia Angélica; Frontera, Jimena Laura; Paz, Dante A.; Gonzalez, María Carolina; Martín, Alejandro; Villanueva, Silvina Stella Maris; Luquet, Carlos Marcelo

doi:10.1016/j.aquatox.2016.07.016

Cited by 20 publications

(13 citation statements)

References 65 publications

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“…Taken together, we presented a new negative regulation loop of cisplatin-induced apoptosis by ST3Gal3, which would contribute to resistance of cisplatin, and provide a precaution for clinic treatment of cisplatin. There were several approaches to reverse chemoresistance, including target to cancer stem cells, inhibition of MDR pathway [32][33][34]. Herein, our data showed that ST3Gal3 down-regulation sensitized high cisplatin-resistant ovarian cancer cells to cisplatin, which could contribute to prevent resistance and relapse of ovarian cancer.…”

Section: Discussionmentioning

confidence: 82%

Alpha2,3-sialyltransferase III knockdown sensitized ovarian cancer cells to cisplatin-induced apoptosis

Wang

Zhang

Lin

et al. 2017

Biochemical and Biophysical Research Communications

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Emerging evidence indicates that β-galactoside-α2,3-sialyltransferase III (ST3Gal3) involves in development, inflammation, neoplastic transformation, and metastasis. However, the role of ST3Gal3 in regulating cancer chemoresistance remains elusive. Herein, we investigated the functional effects of ST3Gal3 in cisplatin-resistant ovarian cancer cells. We found that the levels of ST3Gal3 mRNA differed significantly among ovarian cancer cell lines. HO8910PM cells that have high invasive and metastatic capacity express elevated ST3Gal3 mRNA and are resistant to cisplatin, comparing to SKOV3 cells that have a lower level of ST3Gal3 expression and are more chemosensitive to cisplatin. We found that the expression of ST3Gal3 has reverse correlation with the dosage of cisplatin used in both SKOV3 and HO8910PM cells, and high dose of cisplatin could down-regulate ST3Gal3 expression. We then examined the functional effects of ST3Gal3 knockdown in cancer cell lines using FACS analysis. The number of apoptotic cells was much higher in cells if ST3Gal3 expression was knocked down by siRNA and/or by treating cells with higher dosage of cisplatin in comparison to control cells. Interestingly, in HO8910PM cells with ST3Gal3 knockdown, the levels of caspase 8 and caspase 3 proteins increased, which was more obvious in cells treated with both ST3Gal3 knockdown and cisplatin, suggesting that ST3Gal3 knockdown synergistically enhanced cisplatin-induced apoptosis in ovarian cancer cells. Taken together, these results uncover an alternative mechanism of cisplatin-resistance through ST3Gal3 and open a window for effective prevention of chemoresistance and relapse of ovarian cancer by targeting ST3Gal3.

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Section: Discussionmentioning

confidence: 82%

Alpha2,3-sialyltransferase III knockdown sensitized ovarian cancer cells to cisplatin-induced apoptosis

Wang

Zhang

Lin

et al. 2017

Biochemical and Biophysical Research Communications

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“…Therefore, the effect of MC-LR on the intestinal flora needs to be further studied. Furthermore, studies have also shown that MC-LR could change the glycosylation pattern of the intestinal wall, and suppress the efflux activity of multidrug resistance proteins[ 57 ].…”

Section: Pathological Effect Of Mcs In the Intestinesmentioning

confidence: 99%

Gastrointestinal toxicity induced by microcystins

Huang

Yang

et al. 2018

WJCC

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Microcystins (MCs) are produced by certain bloom-forming cyanobacteria that can induce toxicity in various organs, including renal toxicity, reproductive toxicity, cardiotoxicity, and immunosuppressive effects. It has been a significant global environmental issue due to its harm to the aquatic environment and human health. Numerous investigators have demonstrated that MC exposure can induce a widespread epidemic of enterogastritis with symptoms similar to food poisoning in areas close to lakes. Both in vivo and in vitro studies have provided evidence of positive associations between MC exposure and gastrointestinal toxicity. The toxicity of MCs on the gastrointestinal tract is multidimensional. MCs can affect gastrointestinal barrier function and shift the structure of gut microbiota in different gut regions. Furthermore, MCs can inhibit the secretion of gastrointestinal digestive enzymes and the release of inflammatory cytokines, which affects the expression of immune-related genes in the intestine. The damage of the intestine is closely correlated to MC exposure because the intestine is the main site for the digestion and absorption of nutrients. The damage to the gastrointestinal tract due to MCs was summarized from different aspects, which can be used as a foundation for further exploration of molecular damage mechanisms.

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“…In order to gather more evidence about the possible transport of PST or their metabolites through basolateral ABCC proteins, we have studied the effects of PST1 alone or combined with the ABCC inhibitor MK571. PST1 significantly reduces NRRT50, but blocking ABCCs with MK571 does not increase this effect, as it would be expected, if PST were transported through ABCCs (Bieczynski et al, 2014(Bieczynski et al, , 2016. Thus, PST components would more likely inhibit basolateral ABCC-mediated transport by a non-competitive mechanism.…”

Section: Discussionmentioning

confidence: 90%

“…Many xenobiotic and endobiotic compounds are conjugated with GSH and then exported from the cell through ATP-binding cassette class C (ABCC) transporters (Epel et al, 2008;Omiecinski et al, 2011, for a review). For example, the cyanotoxin microcystin-LR and arsenite have been shown to be detoxified through this mechanism in the middle intestine of Oncorhynchus mykiss and Odontesthes hatchery (Bieczynski et al, 2014(Bieczynski et al, , 2016Painefilú et al, 2019). Since fish are in contact with PST mainly through the diet and drinking, both, the permeability and the biotransformation-excretion capacity of the intestinal epithelium are critical for absorption of toxins and toxicity.…”

Section: Introductionmentioning

confidence: 99%

Effects of paralytic shellfish toxins on the middle intestine of Oncorhynchus mykiss: Glutathione metabolism, oxidative status, lysosomal function and ATP-binding cassette class C (ABCC) proteins activity

Painefilú

Bianchi

Krock

et al. 2020

Ecotoxicology and Environmental Safety

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We studied the absorption, cytotoxicity and oxidative stress markers of Paralytic Shellfish Toxins (PST) from three extracts from Alexandrium catenella and A. ostenfeldii, in middle Oncorhynchus mykiss intestine in vitro and ex vivo preparations. We measured glutathione (GSH) content, glutathione-S transferase (GST), glutathione reductase (GR) and catalase (CAT) enzymatic activity, and lipid peroxidation in isolated epithelium exposed to 0.13 and 1.3 μM PST. ROS production and lysosomal membrane stability (as neutral red retention time 50%, NRRT50) were analyzed in isolated enterocytes exposed to PST alone or plus 3 μM of the ABCC transport inhibitor MK571. In addition, the concentration-dependent effects of PST on NRRT50 were assayed in a concentration range from 0 to 1.3 μM PST. We studied the effects of three different PST extracts on the transport rate of the ABCC substrate DNP-SG by isolated epithelium. The extract with highest inhibition capacity was selected for studying polarized DNP-SG transport in everted and non-everted intestinal segments. We registered lower GSH content and GST activity, and higher GR activity, with no significant changes in CAT activity, lipid peroxidation or ROS level. PST exposure decreased NRRT50 in a concentration-depend manner (IC50 ¼ 0.0045 μM), but PST effects were not augmented by addition of MK571. All the three PST extracts inhibited ABCC transport activity, but this inhibition was effective only when the toxins were applied to the apical side of the intestine and DNP-SG transport was measured at the basolateral side. Our results indicate that PST are absorbed by the enterocytes from the intestine lumen. Inside the enterocytes, these toxins decrease GSH content and inhibit the basolateral ABCC transporters affecting the normal functions of the cell. Furthermore, PST produce a strong cytotoxic effect to the enterocytes by damaging the lysosomal membrane, even at low, non-neurotoxic concentrations.

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Alterations in the intestine of Patagonian silverside ( Odontesthes hatcheri) exposed to microcystin-LR: Changes in the glycosylation pattern of the intestinal wall and inhibition of multidrug resistance proteins efflux activity

Cited by 20 publications

References 65 publications

Alpha2,3-sialyltransferase III knockdown sensitized ovarian cancer cells to cisplatin-induced apoptosis

Alpha2,3-sialyltransferase III knockdown sensitized ovarian cancer cells to cisplatin-induced apoptosis

Gastrointestinal toxicity induced by microcystins

Effects of paralytic shellfish toxins on the middle intestine of Oncorhynchus mykiss: Glutathione metabolism, oxidative status, lysosomal function and ATP-binding cassette class C (ABCC) proteins activity

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