Graphene oxide and reduced graphene oxide induced neural pheochromocytoma-derived PC12 cell lines apoptosis and cell cycle alterations via the ERK signaling pathways

Abstract

Given the novel applications of graphene materials in biomedical and electronics industry, the health hazards of these particles have attracted extensive worldwide attention. Although many studies have been performed on graphene material-induced toxic effects, toxicological data for the effect of graphene materials on the nervous system are lacking. In this study, we focused on the biological effects of graphene oxide (GO) and reduced graphene oxide (rGO) materials on PC12 cells, a type of traditional neural cell line. We found that GO and rGO exerted significant toxic effects on PC12 cells in a dose- and time-dependent manner. Moreover, apoptosis appeared to be a response to toxicity. A potent increase in the number of PC12 cells at G0/G1 phase after GO and rGO exposure was detected by cell cycle analysis. We found that phosphorylation levels of ERK signaling molecules, which are related to cell cycle regulation and apoptosis, were significantly altered after GO and rGO exposure. In conclusion, our results show that GO has more potent toxic effects than rGO and that apoptosis and cell cycle arrest are the main toxicity responses to GO and rGO treatments, which are likely due to ERK pathway regulation.

Germacrone protects against oxygen-glucose deprivation/reperfusion injury by inhibiting autophagy processes in PC12 cells

“…PC12 cell lines, derived from rat adrenal medulla pheochromocytoma, can secrete catecholamine transmitters and have sympathetic neuron characteristics, so they have been widely used in vitro to study of neuron injury mechanism [29,30]. Studies have found that severe cerebral hypoxic I/R injury can induce autophagic death of neurons [31,32].…”

Proinflammatory Effect of Carbon-Based Nanomaterials: In Vitro Study on Stimulation of Inflammasome NLRP3 via Destabilisation of Lysosomes

“…A similar situation could arise for graphene, the 2D layered nanomaterial, which can also be expected to cause mechanical damage to cell membranes via flat and sharp edges [13,14]. Many studies are focused on graphene oxide (GO), which is described as a promising nanomaterial in nanomedicine despite the fact, that many reports point to its potential cytotoxicity [15][16][17][18][19][20][21][22][23][24][25]. However, there are limited data on biological effects of other derivatives such as GP and graphene sheets to which humans are exposed during development, processing or manufacturing [26,27].…”

Cellular Signaling Pathways Activated by Functional Graphene Nanomaterials

“…In particular, the exposition to graphene seemed to increase the mitochondrial membrane permeability, provoking the release of apoptosis-inducing factor. Li et al have demonstrated that the intrinsic apoptosis pathway (mitochondrial-mediated) represented the main death mechanism triggered by pristine G [ 76 ]. In particular, the mitochondrial outer membrane depolarization after graphene exposition occurred in a time-dependent manner and resulted in the increment of expression levels of apoptotic effector enzyme, such as caspase-3.…”