title: Cannabinoid receptor CB1 is involved in nicotine-induced protection against Aβ1-42 neurotoxicity in HT22 cells.
abstract: Emerging evidences suggest that nicotine exerts a neuroprotective effect on Alzheimer's disease (AD), yet the precise mechanism is not fully elucidated. Here, HT22 cells were exposed to amyloid beta protein fragment (Aβ)1-42 to mimic the pathological process of neuron in AD. We hypothesized that cannabinoid receptor CB1 is involved in the nicotine-induced neuroprotection against Aβ1-42 injury in HT22 cells. CB1 expression in HT22 cells was investigated by immunocytochemistry and Western blot. The injury of HT22 cells was evaluated by cellular morphology, cell viability, and lactate dehydrogenase (LDH) release. The apoptosis of HT22 cells was assessed by flow cytometry and expressions of Bcl-2 and Bax. The results demonstrated that nicotine markedly upregulated CB1 expression, increased cell viability, ameliorated cellular morphology, decreased LDH release, and reduced the apoptotic rate of HT22 cells exposed to Aβ1-42 for 24 h, while the blockade of CB1 or the inhibition of protein kinase C (PKC) partially reversed the neuroprotection. Furthermore, the blockade of CB1 reversed nicotine-induced PKC activation in HT22 cells exposed to Aβ1-42. These results suggest that CB1 is involved in the nicotine-induced neuroprotection against Aβ1-42 neurotoxicity, and the neuroprotection may be dependent on the activation of PKC.
authors.affiliation: Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Mingchun
authors.initials: M
authors.lastname: Wu
authors.forename: Ji
authors.initials: J
authors.lastname: Jia
authors.forename: Chong
authors.initials: C
authors.lastname: Lei
authors.forename: Ling
authors.initials: L
authors.lastname: Ji
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Chen
authors.forename: Hanfei
authors.initials: H
authors.lastname: Sang
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D047428:Protein Kinase Inhibitors; D043884:Receptor, Cannabinoid, CB1; C075222:amyloid beta-protein (1-42); D009538:Nicotine; D011493:Protein Kinase C