Methylglyoxal ‐induced neurotoxic effects in primary neuronal‐like cells transdifferentiated from human mesenchymal stem cells: Impact of low concentrations

AbstractIn the last decades, advanced glycation end-products (AGEs) have aroused the interest of the scientific community due to the increasing evidence of their involvement in many pathophysiological processes including various neurological disorders and cognitive decline age related. Methylglyoxal (MG) is one of the reactive dicarbonyl precursors of AGEs, mainly generated as a by-product of glycolysis, whose accumulation induces neurotoxicity. In our study, MG cytotoxicity was evaluated employing a human stem cell-derived model, namely, neuron-like cells (hNLCs) transdifferentiated from mesenchymal stem/stromal cells, which served as a source ofhuman based species-specific “healthy” cells. MG increased ROS production and induced the first characteristic apoptotic hallmarks already at low concentrations (≥10 μM), decreased the cell growth (≥5–10 μM) and viability (≥25 μM), altered Glo-1 and Glo-2 enzymes (≥25 μM), and markedly affected the neuro nal markers MAP-2 and NSE causing their loss at low MG concentrations (≥10 μM). Morphological alterations started at 100 μM, followed by even more marked effects and cell death after few hours (5 h) from 200 μM MG addition. Substantially, most effects occurred as low as 10 μM, concentra tion much lower than that reported from previous observations using different in vitro cell-based models (e.g., human neuroblastoma cell lines, primary animal cells, and human iPSCs). Remarkably, this low effective...
Source: Journal of Applied Toxicology - Category: Toxicology Authors: Tags: RESEARCH ARTICLE Source Type: research