Telomerase activity-independent function of telomerase reverse transcriptase is involved in acrylamide-induced neuron damage

Abstract

Polyacrylamide is used widely in industry, and its decomposition product, acrylamide (ACR), readily finds its way into commonly consumed cosmetics and baked and fried foods. ACR exerts potent neurotoxic effects in human and animal models. Telomerase reverse transcriptase (TERT), the catalytic subunit of telomerase, traditionally has been considered to play an important role in maintaining telomere length. Emerging evidence has shown, however, that TERT plays an important role in neuroprotection by inhibiting apoptosis and excitotoxicity, and by promoting angiogenesis, neuronal survival and neurogenesis, which are closely related to the telomere-independent functions of TERT. We investigated whether and how the TERT pathway is involved in ACR induced neurotoxicity in rat cortical neurons. We found that ACR 1) significantly reduced the viability of cortical neurons as measured by MTT assay, 2) induced neuron apoptosis as revealed by FITC-conjugated Annexin V/PI double staining and flow cytometry (FACS) analysis, 3) elevated expression of cleaved caspase-3, and 4) decreased bcl-2 expression of cortical neurons. ACR also increased intracellular ROS levels in cortical neurons, increased MDA levels and reduced GSH, SOD and GSH-Px levels in mitochondria in a dose-dependent manner. We found that TERT expression in mitochondria was increased by ACR at concentrations of 2.5 and 5.0 mM, but TERT expression was decreased by 10 mM ACR. Telomerase activity, however, was undetectable in rat cortical neurons. Our results suggest that the TERT pathway is involved in ACR induced apoptosis of cortical neurons. TERT also may exert its neuroprotective role in a telomerase activity-independent way, especially in mitochondria.

Poly(methylene blue)-Based Electrochemical Platform for Label-Free Sensing of Acrylamide

“…It has been observed that AM imparts potential genetic, neuro, and reproductive toxicity to humans . AM has a wide range of applications in various industries such as food packaging, paper, and textile and is also used in the separation of proteins. − Deep-fried foods (≥120 °C) contain AM as a result of the Maillard reaction between the reducing sugar and amino acid present in food during food processing/cooking. It has been found that AM is predominantly formed by two pathways, i.e., Strecker synthesis (Schiff base as intermediate) and acrolein (decarboxylation of organic acids). , It has been estimated that exposure humans to AM through food and modern industrialization has reached a range of 0.2–1.9 μg/kg.…”

Acrylamide-derived cytotoxic, anti-proliferative, and apoptotic effects on A549 cells

“…There are other studies which do not specify IC 50 value after acrylamide treatment, but interval of IC 50 value can be inferred from their data. In this manner, IC 50 of acrylamide-treated rat cortical neurons 14 and V79 cells 15 are extrapolated to be 10 and 4–5 mM, respectively. Rat cortical neurons are more resistant to acrylamide, while V79 cells are as sensitive as A549 cells, IC 50 of both are close.…”

Carnosic acid attenuates acrylamide-induced retinal toxicity in zebrafish embryos

“…Previous studies reported that ACR exposure resulted in significantly increased ROS production in neuron-associated cell lines (Albalawi et al, 2018;Pan et al, 2015) and in rat cortical neurons (Zhang et al, 2014). We investigated whether ACR exposure can increase ROS production in zebrafish embryos.…”