All buoyant genera and species of cyanobacteria are at least periodically exposed to higher irradiation during their vertical migration to the surface that usually occurs several times a day. The aim of the study is to assess the influence on cyanobacteria of UVB radiation at realistic environmental intensities. UVB exposure causes damage to the genetic material, cytoskeletal elements, higher sedimentation rates and consequent cell death. In contrast to microcystin producers, the microcystin non-producing strain is more susceptible to the deleterious effects of radiation, with weak recovery ability. The ecological relevance of the results is discussed using data from eleven years’ continuous UVB radiation measurements within the area of Ljubljana city (Slovenia, Central Europe). Our results suggest that increased solar radiation in temperate latitudes can have its strongest effect during cyanobacterial bloom formation in spring and early summer. UVB radiation in this period may significantly influence strain composition of cyanobacterial blooms in favor of microcystin producers.
COBISS.SI-ID: 2888271
Cyanobacterial cytotoxin cylindrospermopsin (CYN) is increasingly found in surface freshwaters, worldwide. It poses a potential threat to humans after chronic exposure as it was shown to be genotoxic in a range of test systems and is potentially carcinogenic. In the present study in HepG2 cells CYN induced formation of DNA double strand breaks (DSBs), morphological changes and cell cycle arrest. The results provide new evidence that CYN is a direct acting genotoxin, causing DSBs, and these facts need to be considered in the human health risk assessment.
COBISS.SI-ID: 2856527
We studied the mechanisms of genotoxicity of the four most abundant HAAs formed in cooked meat: PhIP, MeIQx, 4,8DiMeIQx and IQ in the experimental model with metabolically competent HepG2 cells. The results showed relatively weak genotoxic activity in terms of induction of DNA strand breaks and micronuclei formation. On the other hand all four HAAs induced elevated expression of p53 downstream regulated DNA damage responsive CDKN1A and GADD45α that are indicators of genotoxic and carcinogenic stress. In addition HAAs upregulated the expression of proapoptotic BAX and downregulated expression of antiapoptotic BCL2 genes and their proteins indicating that HAAs may suppress apoptosis. The latter finding is of particular importance as suppression of apoptosis may be a mechanism that possibly contributes to HAAs carcinogenesis.
COBISS.SI-ID: 2827087
Despite improved treatment options, glioblastoma multiforme (GBM) remains the most aggressive brain tumour with the shortest survival. Arsenite (As2O3) is already being used in the treatment of acute promyelocytic leukaemia (APL), yet its effects on GBM have not been evaluated in detail. Using metabolic- and cell viability assays, we demonstrated that long-term CatL silencing significantly increased arsenite cytotoxicity in U87MG spheroids. Silenced CatL increased arsenite-mediated apoptosis in spheroids via elevated p53 expression, Bax/Bcl2 ratio and caspase 3/7 activity, The results have significant translational impact, since stable CatL silencing would enable the application of lower systemic doses of arsenite to achieve the desired cytotoxic effects on GBMs in vivo
COBISS.SI-ID: 2870863
A small library of peptide amides was designed to profile Cathepsin L active site (CatL). Four highly selective sequences with submicromolar affinity toward the targeted CatL were thus identified and two were decorated with an acyloxymethylketone warhead. Despite enabling to favourably distinguish CatL from Cat B, these new irreversible inhibitors did not display any significantly improved selectivity profiles compared to those previously reported.
COBISS.SI-ID: 2768719