Resveratrol inhibits cadmium induced neuronal apoptosis by modulating calcium signalling pathway via regulation of MAPK/mTOR network

Abstract

<p>Cadmium, a toxic environmental contaminant, induces oxidative stress leading to various neurodegenerative disorders, where it interferes with homeos-tasis of intracellular free calcium ([Ca<sup>2+</sup>]i), leading to cellular damage and apoptosis. We investigated whether resveratrol, a plant-derived antioxidant could offer protection against cadmium-induced neuroapoptosis. Primary cortical neurons were exposed to cadmium (10 or 20 µM) with/without prior exposure to resveratrol (5, 10 or 20 µM) for 12 hours and unexposed cells served as control. Resveratrol caused marked reduction in cadmium-induced neuronal apoptosis and down-regulated caspase-3 expressions. Cadmium-induced marked elevations in reactive oxygen species, and ([Ca<sup>2+</sup>]i) levels were potentially reduced by resveratrol. Resveratrol effectively regulated the alterations observed in the activation levels of mitogen-activated protein kinases (MAPKs) and proteins of mammalian target of rapamycin (mTOR) pathways. Thus, resveratrol effectively protected the cortical neurons exposed to cadmium by modulating the ([Ca<sup>2+</sup>]i) levels and regulating the MAPK/mTOR pathways.</p><p> </p>

Resveratrol protects against cadmium chloride‐induced hippocampal neurotoxicity by inhibiting ER stress and GAAD 153 and activating sirtuin 1/AMPK/Akt

“…Trans ‐RES (3,5,4‐trihydroxy‐ trans ‐stilbene), a polyphenolic phytoalexin found in grapes, cranberries, and peanuts, is an excellent neuroprotective agent in both animals and humans . In various animal models of neurodegeneration, RES inhibited neural cell apoptosis and improved learning and memory function with many thanks to its antioxidant and ROS scavenging potentials and its ability to modulate numerous signaling pathways including Ca 2+ , ERK1/2, and JNK . Recently, we have shown that RES prevented tau hyperphosphorylation and memory deficits in cadmium chloride (CdCl 2 )‐induced rat's model of neurodegeneration by increasing GSH levels, inhibition of ROS, downregulation of Bax, and upregulation of Bcl‐2, mediated by activation of AMPK/PI3K/Akt axis activity .…”

“…[19][20][21][22][23][24] In various animal models of neurodegeneration, RES inhibited neural cell apoptosis and improved learning and memory function with many thanks to its antioxidant and ROS scavenging potentials and its ability to modulate numerous signaling pathways including Ca 2+ , ERK1/2, and JNK. [22][23][24][25] Recently, we have shown that RES prevented tau hyperphosphorylation and memory deficits in cadmium chloride (CdCl 2 )induced rat's model of neurodegeneration by increasing GSH levels, inhibition of ROS, downregulation of Bax, and upregulation of Bcl-2, mediated by activation of AMPK/PI3K/Akt axis activity. 26 Also, RES prevented neural apoptosis and preserved motor and memory function in rotenone-induced Parkinson's disease and postoperative cognitive dysfunction animal models by inhibition of ER stress and UPRrelated proteins.…”

Protective effects of Vitis vinifera (grapes) and one of its biologically active constituents, resveratrol, against natural and chemical toxicities: A comprehensive review

“…Administration of GSE normalized all these biomarkers (El‐Tarras, Attia, Soliman, Awady, & Amin, ). Lin, Peng, Yang, and Mi () exposed primary cortical neurons to Cd (10 and 20 μM) and RSV (5, 10, and 20 μM) for 12 hr. RSV caused noticeable decrease in neuronal apoptosis and caspase 3 induced by Cd.…”

“…It also reduced ROS and Ca 2+ levels, along with regulation of alterations in MAPKinase pathway. Therefore, this could be a probable neuroprotective mechanism of RSV against Cd (Lin et al, ).…”

Floroquinone induces apoptosis and inhibits carcinoma growth in mouse tumor xenograft model of anaplastic thyroid cancer

“…The cells were incubated with floroquinone for 48 hours, fixed in ice-cold paraformaldehyde, rinsed in PBS and subsequently stained with 4,6-diamidino-2-phenylindole (DAPI) for 30 min at 37°C. A fluorescent microscope was used for the analysis of the nuclear fragmentation in DAPI-stained cells (Lin et al, 2015). TUNEL kit (Chemic on, USA) was used for performing TUNEL assay according to the manufacturer's instructions.…”