Coal extraction causes sediment toxicity in aquatic environments in Santa Catarina, Brazil

This study evaluated water parameters in ponds affected by coal extraction. Allium cepa assay was used to measure genotoxicity/mutagenicity of the sediment. Samples were collected from four ponds in the southern state of Santa Catarina. Water temperature, pH, dissolved oxygen, conductivity and turbidity were measured. Sediments were analyzed for heavy metals. Elutriate samples were prepared at a ratio of 1:4 sediment:water. Allium cepa bulbs were placed in samples prepared from each pond, with ultrapure water used as negative control and methyl methane sulfonate as positive control. Root length, mitotic index, chromosomal aberrations, micronuclei, and nuclear abnormalities were measured. The pH of two ponds, as well as electrical conductivity and dissolved oxygen of all ponds were below the minimum limits set by Brazilian regulation. All heavy metals analyzed were found in all sediment samples, but only Cd concentration was above the legal limit set by Brazilian law. Allium cepa root growth for samples from Ponds 1, 2, and 4 was significantly lower than the negative control. Meristematic cells exposed to elutriate samples showed no significant changes in cell division. There was a significant increase in total chromosomal aberrations in all treated samples in comparison with the negative control. This study demonstrates that even low concentrations of heavy metals can damage exposed biota, possibly due to synergistic effects. We also found the A. cepa bioassay to be a simple and useful tool for genotoxicity/mutagenicity analyses, and recommend its use for environmental monitoring and management in areas influenced by mining activities

Protein disulfide isomerase-mediated transcriptional upregulation of Nox1 contributes to vascular dysfunction in hypertension

Nox1 signaling is a causal key element in arterial hypertension. Recently, we identified protein disulfide isomerase A1 (PDI) as a novel regulatory protein that regulates Nox1 signaling in VSMCs. Spontaneously hypertensive rats (SHR) have increased levels of PDI in mesenteric resistance arteries compared with Wistar controls; however, its consequences remain unclear. Herein, we investigated the role of PDI in mediating Nox1 transcriptional upregulation and its effects on vascular dysfunction in hypertension. We demonstrate that PDI contributes to the development of hypertension via enhanced transcriptional upregulation of Nox1 in vascular smooth muscle cells (VSMCs). We show for the first time that PDI sulfenylation by hydrogen peroxide contributes to EGFR activation in hypertension via increased shedding of epidermal growth factor-like ligands. PDI also increases intracellular calcium levels, and contractile responses induced by ANG II. PDI silencing or pharmacological inhibition in VSMCs significantly decreases EGFR activation and Nox1 transcription. Overexpression of PDI in VSMCs enhances ANG II-induced EGFR activation and ATF1 translocation to the nucleus. Mechanistically, PDI increases ATF1-induced Nox1 transcription and enhances the contractile responses to ANG II. Herein we show that ATF1 binding to Nox1 transcription putative regulatory regions is augmented by PDI. Altogether, we provide evidence that HB-EGF in SHR resistance vessels promotes the nuclear translocation of ATF1, under the control of PDI, and thereby induces Nox1 gene expression and increases vascular reactivity. Thus, PDI acts as a thiol redox-dependent enhancer of vascular dysfunction in hypertension and could represent a novel therapeutic target for the treatment of this disease