Endoplasmic reticulum stress in murine liver and kidney exposed to microcystin-LR

The Kidney Vero-E6 Cell Line: A Suitable Model to Study the Toxicity of Microcystins

“…The observation that MCLR induced the destructuring of the endoplasmic reticulum (ER) suggested that this organelle is involved in MCLR toxicity in Vero cell line [29,30]. The involvement of the ER in MCLR-mediated toxicity was also previously reported in mouse kidney and liver [37]. At higher concentrations, MCLR induced the disruption of the plasma membrane, lysosomes and mitochondria of Vero cells [29,30].…”

A proteomic analysis of prenatal transfer of microcystin-LR induced neurotoxicity in rat offspring

“…Pdia3 can act as molecular chaperones by inhibiting the aggregation of unfolded/misfolded proteins at the ER. Some studies showed that MCs could trigger oxidative stress and ER stress [60,61]. Subsequently, cellular mechanisms to diminish ER stress can be activated through up-regulation of molecular chaperones, which could enhance ER protein folding capacity and increase activity of ER-associated degradation pathways for the removal of misfolded proteins [62].…”

Mechanisms of Microcystin-induced Cytotoxicity and Apoptosis

“…It has been reported that over-expression of CHOP can lead to translocation of Bax protein from the cytosol to the mitochondria and decrease in Bcl-2 protein and finally trigger the mitochondrial pathway. MC-LR significantly improved mRNA and protein expression of CHOP and cleaved caspase-12 in mouse liver, whereas it inhibited expression of CHOP and caspase-12 in kidney [151]. The expression levels of GRP78, which may stabilize protein folding under ERS and protect cells from apoptosis, were significantly increased in MC-RR-treated mouse liver, but no obvious alteration was found in CHOP expression [152].…”

“…the unfolded protein response (UPR), including upregulation of molecular chaperones (GRP78 and GRP94), enhancement of ER protein folding capacity, decrease in protein synthesis to diminish ER load or increased activity of ER-associated protein degradation (ERAD) pathways for the removal of misfolded proteins [32,150]. UPR signaling affords the cell a "window of opportunity" for stress resolution and thus temperate ERS can relieve cellular dysfunction and increase the possibility for cell survival; however, serious and/or prolonged ERS leads to apoptosis, which is mediated by transcriptional induction of C/EBP homologous protein (CHOP) and/or by a caspase-12-dependent pathway [150,151]. ER-targeted stress can also activate Ca 2+ efflux from the ER; this Ca 2+ is then redistributed to the mitochondria and leads to apoptosis [148].…”