Abstract
Cylindrospermopsin (CYN) is a cyanotoxin that has been recognised as an emerging potential public health risk. Although CYN toxicity has been demonstrated, the mechanisms involved have not been fully characterised. To identify some key pathways related to this toxicity, we studied the transcriptomic profile of human intestinal Caco-2 cells exposed to a sub-toxic concentration of CYN (1.6 µM for 24hrs) using a non-targeted approach. CYN was shown to modulate different biological functions which were related to growth arrest (with down-regulation of cdkn1a and uhrf1 genes), and DNA recombination and repair (with up-regulation of aptx and pms2 genes). Our main results reported an increased expression of some histone-modifying enzymes (histone acetyl and methyltransferases MYST1, KAT5 and EHMT2) involved in chromatin remodelling, which is essential for initiating transcription. We also detected greater levels of acetylated histone H2A (Lys5) and dimethylated histone H3 (Lys4), two products of these enzymes. In conclusion, CYN overexpressed proteins involved in DNA damage repair and transcription, including modifications of nucleosomal histones. Our results highlighted some new cell processes induced by CYN.
Highlights
The toxin cylindrospermopsin (CYN) is produced by several freshwater cyanobacteria species such as Cylindrospermopsis raciborskii, which is nowadays common throughout the world, as its recent occurrence in temperate regions attests [1,2]
From the ‘‘filtered data’’, considering an fold change (FC) greater than 2 or less than 0.5, and a P - value,0.05, we identified a set of 572 genes with a differential expression between CYN treatment and control samples
Previous studies reported a concentration-dependent decrease in cell viability on the same cell model with IC50 ranging from 5 to 50 mM probably due to the conditions used for the cytotoxicity test and if cells were differentiated or not [12,13,28]
Summary
The toxin cylindrospermopsin (CYN) is produced by several freshwater cyanobacteria species such as Cylindrospermopsis raciborskii, which is nowadays common throughout the world, as its recent occurrence in temperate regions attests [1,2]. Unlike other cyanobacterial toxins which are generally sequestered inside cyanobacteria until death, CYN can be released in water during blooms (up to 90% of the CYN produced) [5,6]. Several cases of human intoxications due to CYN water contamination have been reported in Australia and Brazil [8,9]. These events revealed that CYN may induce various injuries, including gut damage, occasionally leading to death. This cyanobacterial toxin has been recognised as a potential public health risk in several countries [10]
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