Microcystin-LR stabilizes c-myc protein by inhibiting protein phosphatase 2A in HEK293 cells

Fan, Huihui; Cai, Yan; Xie, Ping; Xiao, Wuhan; Chen, Jun; Ji, Wei; Zhao, Sujuan

doi:10.1016/j.tox.2014.02.015

Cited by 25 publications

(16 citation statements)

References 47 publications

(55 reference statements)

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“…At the same time, the c-myc gene is the best-studied member of the myc oncogene family, which encodes a transcriptional regulator involved in carcinogenesis. Even though the detailed mechanism of genital carcinoma-promoting activity of MCs has not been well elucidated, it has been suggested to arise from their inhibition of PP1/2A, which negatively regulated NF-B and several mitogen-activated protein kinases (MAPK) [28,56,82,125,126]. Once activated, NF-B and MAPK are transferred to the nucleus, where it could activate c-fos, c-jun, c-myc and other proto-oncogenes, which initiate transcription of genes necessary for growth and differentiation.…”

Section: Reproductive Tumorsmentioning

confidence: 99%

A review of reproductive toxicity of microcystins

Chen

Zhang

et al. 2016

Journal of Hazardous Materials

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288

126

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Section: Reproductive Tumorsmentioning

confidence: 99%

A review of reproductive toxicity of microcystins

Chen

Zhang

et al. 2016

Journal of Hazardous Materials

Self Cite

288

126

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“…Li et al [87] also observed that the exposure to MC extracts greatly induced the expression of proto-oncogenes c-fos, c-jun and c-myc in mouse liver, kidney and testis, making it a possible mechanism for MC tumor-promoting activity. Recently Fan et al [88] suggested that hepatic tumorigenesis may also be related with MC-LR stimulation of proto-oncogene cmyc transcription and the inhibition of protein phosphatase PP2A activity, which has a stabilization effect on c-myc protein, by altering the phosphorylation status of serine 62. The higher susceptibility of liver to MCs may be in part related with the OATP transport system highly abundant in hepatocytes thereby favoring the uptake of the molecule and its tumor promotion activity.…”

Section: Tumor Promotionmentioning

confidence: 99%

New Insights on the Mode of Action of Microcystins in Animal Cells - A Review

Valério¹,

Vasconcelos²,

Campos

2016

MRMC

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Microcystins (MCs) are the most commonly occurring hepatotoxins produced by cyanobacteria. The inhibition of PP2A is widely assumed as the principal mechanism of toxicity of MCs, however recently it has been found that MC modulates PP2A activity not only by direct inhibition of its activity, but also by regulating its expression. Nevertheless the mechanisms of toxicity of MCs seem to be more complex to interpret than expected. The induction of some cellularmolecular mechanisms appears to be biphasic in time and concentration of MC and in most cases related with the intracellular ROS generation. These intracellular ROS levels cause oxidative stress which leads to changes in several markers of MC-LR-induced oxidative stress ultimately resulting in apoptosis or cell damage and also genotoxicity. MCs can also induce severe changes in the cytoskeleton elements: microfilaments, intermediate filaments and microtubules, which results in changes in the cytoskeleton architecture and cell viability. There are also indications that there are second messengers involved in MC-LR mediated cytotoxicity and apoptosis. Different congeners of these toxins induce different degrees of responses in the cell, assumed to be related with the capacity of toxin internalization, affinity towards PP1 and PP2A, and the ability to cause oxidative stress. MCs have also been implicated in neurotoxicity and in damages in reproductive organs. The regulation of transcription factors and proto-oncogenes by MC is the mode of action of MCs tumor promotion. This review summarizes mainly the findings from the last five years about the molecular mechanisms behind MC toxicity in animal cells.

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“…Even the chronic exposure to low concentrations of MCs also can promote tumor growth. The International Agency for Research on Cancer (IARC) has classified MC-LR as a possible carcinogen because of its potential carcinogenic activity [10]. To reduce MC-LR risks, the World Health Organization (WHO) has proposed a provisional guideline of 1 µg/L MCs in drinking water and this guideline level has been adopted in legislation in many countries such as South America, Australasia, Europe and China [11].…”

Section: Introductionmentioning

confidence: 99%

Aerobic removal of microcystin-LR by a novel native effective bacterial community designated as YFMCD4 isolated from Lake Taihu

Guo

Huang

Massey

et al. 2018

Preprint

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12 Microcystins (MCs) are a group of monocyclic heptapeptide hepatotoxins produced by species of 13 cyanobacteria. MC-LR is the most toxic and frequently detected MCs variant in water, which 14 poses a great threat to the natural ecosystem and public health. It's important to seek 15 environment-friendly and cost-efficient methods to remove MC-LR. To investigate the MC-16 degrading capacities of a novel indigenous bacterial community designated as YFMCD4 and the 17 influence of environmental factors including various temperatures, MC concentrations and pH on 18 the MC-degrading activities, the concentration of MC-LR was measured by high performance 19liquid chromatography. In addition, the MC-degrading mechanism containing the degradation 20 pathway and products of YFMCD4 was studied using HPLC coupled with an ultra-high 21 resolution LTQ Orbitrap Velos Pro ETD mass spectrometry equipped with electrospray 22 ionization interface. The data showed MC-LR can be removed at the maximum rate of 0.5 23 µg/(ml·h) by YFMCD4 containing Alcaligenes faecalis and Stenotrophomonas acidaminiohila. 24The MC-degrading rates of YFMCD4 were significantly affected by different temperatures, pH 25 and MC-LR concentrations. Two intermediates of a tetrapeptide and Adda appeared in the 26 degradation process. These results illustrate that the novel bacterial community YFMCD4 can 27 remove MC-LR effectively and completely, which indicates YFMCD4 possesses a significant 28 potential to be used in bioremediation of water bodies contaminated by MC-LR. 29 3 47 MC-LR is very stable and resistant to many natural factors including extreme pH, high 48 temperature and sunlight in the environment owing to the cyclic structure [3, 6, 12]. Moreover, 49 MC-LR can be accumulated in aquatic organisms and food crops representing a health hazard to 50 human and animals through food chains [13]. It is very important to reduce MC-LR 51 concentration in freshwater ecosystem. However, conventional drinking water treatments have 52 limited efficacy in removing MC-LR. Some physical and chemical methods containing 53 ozonation, chlorination, photocatalysis and electrolysis have been proposed for MC-LR 54 elimination from drinking water. However, all these methods have certain limitations in terms of 55 high operating costs, low efficacy and harmful by-products [3, 6, 14, 15]. It's desirable that 56investigators seek other environmentally-benign and cost-efficient methods and technologies to 57 remove MC-LR found in water bodies [3, 6,[14][15][16][17]. 58Several previous investigations demonstrated that microbial biodegradation may be one of 59 the most environmentally-friendly, effective and promising treatment methods for removing 60 MC-LR in natural waters, since it can detoxify MC-LR and don't generated any apparent 61 potential harmful by-products [3, 6,[14][15][16][17]. A few MC-degrading pure bacterial strains have 62 been isolated, identified and had their mechanisms reported, and most of the isolated MC-63 degrading bacteria were limited to the family S...

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Microcystin-LR stabilizes c-myc protein by inhibiting protein phosphatase 2A in HEK293 cells

Cited by 25 publications

References 47 publications

A review of reproductive toxicity of microcystins

A review of reproductive toxicity of microcystins

New Insights on the Mode of Action of Microcystins in Animal Cells - A Review

Aerobic removal of microcystin-LR by a novel native effective bacterial community designated as YFMCD4 isolated from Lake Taihu

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