Nicotine exerts neuroprotective effects against β-amyloid-induced neurotoxicity in SH-SY5Y cells through the Erk1/2-p38-JNK-dependent signaling pathway

Abstract

Epidemiological data have indicated that smoking tobacco can decrease the risk of developing Alzheimer's disease (AD). Nicotine, a main component of tobacco, has been shown to have therapeutic effects in AD. The aim of the present study was to assess the neuroprotective effects of nicotine against toxicity induced by β-amyloid (Aβ) in relation to cell apoptosis, and to elucidate the role of the activation of the Erk1/2-p38-JNK pathway and the modulation of anti-apoptotic proteins in the nicotine-induced neuroprotective effects. We performed in vitro and in vivo experiments using SH-SY5Y cells and C57BL/6 mice, respectively. The effects of nicotine on cell apoptosis were determined by flow cytmetry and microscopic observation. The effects of nicotine on the expression of anti-apoptotic proteins were also determined by western blot analysis. Our results demonstrated that nicotine protected the SH-SY5Y cells against Aβ25-35-induced toxicity by inhibiting apoptosis and upregulating the expression of anti-apoptotic proteins. As shown by our in vivo experiments, nicotine effectively ameliorated the impairment in spatial working memory induced by Aβ25-35; this was confirmed by a Morris water maze navigation test and further supported by the upregulation of Bcl-2 in the hippocampus of Aβ25-35-injected mice treated with nicotine. The phosphorylation of Erk1/2, p38 and JNK increased following treatment with nicotine in the SH-SY5Y cells, whereas caspase-3 activation was inhibited by treatment with nicotine prior to exposure to Aβ25-35. Of note, these effects of nicotine against Aβ25-35-induced damage were abolished by inhibitors of Erk1/2, p38 and JNK phosphorylation. These findings suggest that nicotine prevents Aβ25-35-induced neurotoxicity through the inhibition of neuronal apoptosis, and may thus prove to be a potential preventive or therapeutic agent for AD.

The neuroprotective effect of nicotine in Parkinson’s disease models is associated with inhibiting PARP-1 and caspase-3 cleavage

“…Several signaling pathways that promote cell survival are enhanced by stimulating nAChR, including the Src family-PI3 K-AKT pathway, with subsequent upregulation of Bcl-2 and Bcl-x, JAK2/STAT3 and MEK/ERK ( Kawamata & Shimohama, 2011 ). Nicotine can protect SH-SY5Y cells from other types of insults, such as beta-amyloid toxicity, through Erk1/2-p38-JNK-dependent signaling pathways ( Xue et al, 2014 ). However, there are no published studies investigating the role of PARP-1 or caspase in the neuroprotective effects of nicotine in PD disease models.…”

Interleukin 6 trigged ataxia-telangiectasia mutated activation facilitates lung cancer metastasis via MMP-3/MMP-13 up-regulation

“…In vivo cell migration ability and the expression of MMP-3/MMP-13 in lung were determined via H&E and Immunohistochemistry staining [ 68 ]. Briefly, free-floating lung sections (4 μM) were obtained using a slicing system (Leica RM2135).…”

Nicotine‐mediated neuroprotection of rat spinal networks against excitotoxicity

“…nAChRs are implicated in neuroprotection mechanisms against acute cell distress (Bencherif, ) induced by excitotoxicity, namely a process of over‐activation of glutamate receptors considered as a paradigm of neurodegeneration (Choi, , ). Nicotine‐mediated neuroprotection has been reported in vitro (Garrido, King‐Pospisil, Son, Hennig, & Toborek, ), in vivo (Xue, Liu, Zhang, & Gao, ) and in epidemiological studies (Quik, Perez, & Bordia, ), suggesting potential strategies to contrast neuronal death. On brainstem motoneurons, nicotine protects against excitotoxicity to block reactive oxygen species (ROS) and by normalizing mitochondrial metabolism (Corsini, Tortora, & Nistri, ; Tortora, Corsini, & Nistri, ).…”