Whole genome mRNA transcriptomics analysis reveals different modes of action of the diarrheic shellfish poisons okadaic acid and dinophysis toxin-1 versus azaspiracid-1 in Caco-2 cells

被引：17

作者：

Bodero, Marcia ^{[1
,2
]}

Hoogenboom, Ron L. A. P. ^{[1
]}

Bovee, Toine F. H. ^{[1
]}

Portier, Liza ^{[1
]}

de Haan, Laura ^{[2
]}

Peijnenburg, Ad ^{[1
]}

Hendriksen, Peter J. M. ^{[1
]}

机构：

[1] RIKILT Wageningen Univ &Research, Akkerrnaalsbos 2, NL-6708 WB Wageningen, Netherlands

[2] Wageningen Univ &Research, Div Toxicol, Stippeneng 4, NL-6708 WE Wageningen, Netherlands

来源：

TOXICOLOGY IN VITRO | 2018年 / 46卷

关键词：

Okadaic acid; Dinophysis toxin-1; Azaspiracid-1; Mode of action; Transcriptomics; Caco-2; cells; ENDOPLASMIC-RETICULUM STRESS; COLLAGENASE GENE-EXPRESSION; CHOLESTEROL-BIOSYNTHESIS; MARINE TOXINS; ORGAN DAMAGE; TOXICITY; ACTIVATION; HYPOXIA; METALLOTHIONEIN; PROLIFERATION;

D O I：

10.1016/j.tiv.2017.09.018

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

A study with DNA microarrays was performed to investigate the effects of two diarrhetic and one azaspiracid shellfish poison, okadaic acid (OA), dinophysistoxin-1 (DTX-1) and azaspiracid-1 (AZA-1) respectively, on the whole-genome mRNA expression of undifferentiated intestinal Caco-2 cells. Previously, the most responding genes were used to develop a dedicated array tube test to screen shellfish samples on the presence of these toxins. In the present study the whole genome mRNA expression was analyzed in order to reveal modes of action and obtain hints on potential biomarkers suitable to be used in alternative bioassays. Effects on key genes in the most affected pathways and processes were confirmed by qPCR. OA and DTX-1 induced almost identical effects on mRNA expression, which strongly indicates that OA and DTX-1induce similar toxic effects. Biological interpretation of the microarray data indicates that both compounds induce hypoxia related pathways/processes, the unfolded protein response (UPR) and endoplasmic reticulum (ER) stress. The gene expression profile of AZA-1 is different and shows increased mRNA expression of genes involved in cholesterol synthesis and glycolysis, suggesting a different mode of action for this toxin. Future studies should reveal whether identified pathways provide suitable biomarkers for rapid detection of DSPs in shellfish.

引用

页码：102 / 112

页数：11

共 69 条

[1] Low Levels of GSTA1 Expression Are Required for Caco-2 Cell Proliferation [J].

Adnan, Humaira ;

Quach, Holly ;

MacIntosh, Kimberley ;

Antenos, Monica ;

Kirby, Gordon M. .

PLOS ONE, 2012, 7 (12)

[2] First identification of azaspiracid and spirolides in Mesodesma donacium and Mulinia edulis from Northern Chile [J].

Alvarez, Gonzalo ;

Uribe, Eduardo ;

Avalos, Paulo ;

Marino, Carmen ;

Blanco, Juan .

TOXICON, 2010, 55 (2-3) :638-641

[3] Relative toxicity of dinophysistoxin-2 (DTX-2) compared with okadaic acid, based on acute intraperitoneal toxicity in mice [J].

Aune, Tore ;

Larsen, Stig ;

Aasen, John A. B. ;

Rehmann, Nils ;

Satake, Masayuki ;

Hess, Philipp .

TOXICON, 2007, 49 (01) :1-7

[4]

Berridge MV, 2005, BIOTECHNOL ANN REV, V11, P127, DOI 10.1016/S1387-2656(05)11004-7

[5] INHIBITORY EFFECT OF A MARINE-SPONGE TOXIN, OKADAIC ACID, ON PROTEIN PHOSPHATASES - SPECIFICITY AND KINETICS [J].

BIALOJAN, C ;

TAKAI, A .

BIOCHEMICAL JOURNAL, 1988, 256 (01) :283-290

[6] A Perspective on the Toxicology of Marine Toxins [J].

Botana, Luis M. .

CHEMICAL RESEARCH IN TOXICOLOGY, 2012, 25 (09) :1800-1804

[7] Tailored Microarray Platform for the Detection of Marine Toxins [J].

Bovee, T. F. H. ;

Hendriksen, P. J. M. ;

Portier, L. ;

Wang, S. ;

Elliott, C. T. ;

van Egmond, H. P. ;

Nielen, M. W. F. ;

Peijnenburg, A. A. C. M. ;

Hoogenboom, L. A. P. .

ENVIRONMENTAL SCIENCE & TECHNOLOGY, 2011, 45 (20) :8965-8973

[8] Comparative study of the use of neuroblastoma cells (Neuro-2a) and neuroblastorna x glioma hybrid cells (NG108-15) for the toxic effect quantification of marine toxins [J].

Canete, Elisabeth ;

Diogene, Jorge .

TOXICON, 2008, 52 (04) :541-550

[9] A molecular web: endoplasmic reticulum stress, inflammation, and oxidative stress [J].

Chaudhari, Namrata ;

Talwar, Priti ;

Parimisetty, Avinash ;

d'Hellencourt, Christian Lefebvre ;

Ravanan, Palaniyandi .

FRONTIERS IN CELLULAR NEUROSCIENCE, 2014, 8

[10] Activation of protein phosphatase 5 by limited proteolysis or the binding of polyunsaturated fatty acids to the TPR domain [J].

Chen, MX ;

Cohen, PTW .

FEBS LETTERS, 1997, 400 (01) :136-140

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