Cellular transport of microcystin-LR in rainbow trout (Oncorhynchus mykiss) across the intestinal wall: Possible involvement of multidrug resistance-associated proteins

Bieczynski, Flavia; Anna, Julieta S. De; Pírez, Macarena; Brena, Beatríz M.; Villanueva, Silvina Stella Maris; Luquet, Carlos Marcelo

doi:10.1016/j.aquatox.2014.05.003

Cited by 29 publications

(23 citation statements)

References 70 publications

(88 reference statements)

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“…More than 80 structural variants have been identified, differing primarily in two L -amino acids. The major isoforms are microcystin-LR (MC-LR), microcystin-RR, and microcystin-YR [ 2 ]. Toxins are released into the surrounding medium during senescence and lysis of bloom cells, which affect many organisms, from terrestrial mammals to algae.…”

Section: Introductionmentioning

confidence: 99%

Activity and Transcriptional Responses of Hepatopancreatic Biotransformation and Antioxidant Enzymes in the Oriental River Prawn Macrobrachium nipponense Exposed to Microcystin-LR

Yuan

Wang

et al. 2015

Toxins

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Microcystins (MCs) are a major group of cyanotoxins with side effects in many organisms; thus, compounds in this group are recognized as potent stressors and health hazards in aquatic ecosystems. In order to assess the toxicity of MCs and detoxification mechanism of freshwater shrimp Macrobrachium nipponense, the full-length cDNAs of the glutathione S-transferase (gst) and catalase (cat) genes were isolated from the hepatopancreas. The transcription level and activity changes in the biotransformation enzyme (glutathione S-transferase (GST)) and antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx)) in the hepatopancreas of M. nipponense exposed to MC-LR (0.2, 1, 5, and 25 μg/L) for 12, 24, 72 and 96 h were analyzed. The results showed that the isolated full-length cDNAs of cat and gst genes from M. nipponense displayed a high similarity to other crustaceans, and their mRNAs were mainly expressed in the hepatopancreas. MC-LR caused significant increase of GST activity following 48–96 h (p < 0.05) and an increase in SOD activity especially in 24- and 48-h exposures. CAT activity was activated when exposed to MC-LR in 12-, 24- and 48-h exposures and then it was inhibited at 96-h exposure. There was no significant effect on GPx activity after the 12- and 24-h exposures, whereas it was significantly stimulated after the 72- and 96-h exposures (p < 0.05). The transcription was altered similarly to enzyme activity, but the transcriptional response was generally more immediate and had greater amplitude than enzymatic response, particularly for GST. All of the results suggested that MC-LR can induce antioxidative modulation variations in M. nipponense hepatopancreas in order to eliminate oxidative damage.

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Section: Introductionmentioning

confidence: 99%

Activity and Transcriptional Responses of Hepatopancreatic Biotransformation and Antioxidant Enzymes in the Oriental River Prawn Macrobrachium nipponense Exposed to Microcystin-LR

Yuan

Wang

et al. 2015

Toxins

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“…Moreover, Schwarzenberger et al (2014) recently reported that the increases of permeases gene expression were detected in the tolerant Daphnia clone, leading to higher production of transporter protein, which subsequently results in a stronger excretion of microcystins from the cells. Given that excreting microcystins process is energy-dependent (Campos and Vasconcelos, 2010;Bieczynski et al, 2014), it is reasonable that elevated Dm-AK expression and ATP content may promote microcystins excretion. Hence, our results together with results of Schwarzenberger et al (2009Schwarzenberger et al ( , 2014 could partly explain why subsequent offspring had higher fitness when the previous generation had been exposed to toxic Microcystis.…”

Section: Discussionmentioning

confidence: 99%

Arginine kinase in the cladoceran Daphnia magna: cDNA sequencing and expression is associated with resistance to toxic Microcystis

et al. 2015

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“…3). It is known to us that MCs themselves cannot readily diffuse through the plasma membrane and enter cells without the help of any transporter located in the cell membrane due to their relatively higher molecular weight (900-1100 Da) and moderate hydrophobicity (Komatsu et al, 2007;Bieczynski et al, 2014). Previous studies have found that MC-LR is usually transported into cells via OATPs; for example, OATP1B1 and OATP1B3 are the most efficient MC-LR transporters in human hepatocytes (Hagenbuch and Gui, 2008;Kalliokoski and Niemi, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…Transporters such as P-glycoprotein (Pgp, MDR1, ABCB1) and multidrug resistance proteins (MRPs, ABCC) are members of the ATP-binding cassette (ABC) superfamily, and they have been identified in tumor cells to resist drugs or chemicals by immediate discharge and therefore prevention of cell abidance of the drugs or chemicals (Bolhuis et al, 1997;Keppler et al, 2011;Bieczynski et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Altered cellular metabolism of HepG2 cells caused by microcystin-LR

Feng

Jiang

et al. 2017

Environmental Pollution

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This study aimed to evaluate the possible effects of microcystin-LR (MC-LR) exposure on the metabolism and drug resistance of human hepatocellular carcinoma (HepG2) cells. For this purpose, we first conducted an experiment to make sure that MC-LR could penetrate the HepG2 cell membrane effectively. The transcriptional levels of phase I (such as CYP2E1, CYP3A4, and CYP26B1) and phase II (such as EPHX1, SULTs, and GSTM) enzymes and export pump genes (such as MRP1 and MDR1) were altered by MC-LR-exposure for 24 h, indicating that MC-LR treatment may destabilize the metabolism of HepG2 cells. Further research showed that the CYP inducers omeprazole, ethanol, and rifampicin inhibited cell viability, in particular, ethanol, a CYP2E1 inducer, induced ROS generation, lipid peroxidation, and apoptosis in HepG2 cells treated with MC-LR. The CYP2E1 inhibitor chlormethiazole inhibited ROS generation, mitochondrial membrane potential loss, caspase-3 activity, and cytotoxicity caused by MC-LR. Meanwhile, the results also showed that co-incubation with the ROS scavenger l-ascorbic acid and MC-LR decreased ROS levels and effectively prevented apoptosis. These findings provide an interesting mechanistic explanation of cellular metabolism associated with MC-LR, i.e., MC-LR-exposure exerted toxicity on HepG2 cells and induced apoptosis of HepG2 cells via promoting CYP2E1 expression and inducing excessive ROS in HepG2 cells.

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Cellular transport of microcystin-LR in rainbow trout (Oncorhynchus mykiss) across the intestinal wall: Possible involvement of multidrug resistance-associated proteins

Cited by 29 publications

References 70 publications

Activity and Transcriptional Responses of Hepatopancreatic Biotransformation and Antioxidant Enzymes in the Oriental River Prawn Macrobrachium nipponense Exposed to Microcystin-LR

Activity and Transcriptional Responses of Hepatopancreatic Biotransformation and Antioxidant Enzymes in the Oriental River Prawn Macrobrachium nipponense Exposed to Microcystin-LR

Arginine kinase in the cladoceran Daphnia magna: cDNA sequencing and expression is associated with resistance to toxic Microcystis

Altered cellular metabolism of HepG2 cells caused by microcystin-LR

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