title: Resistin protection against endogenous Aβ neuronal cytotoxicity from mitochondrial pathway.
abstract: Neurotoxicity of amyloid β (Aβ) plays an important role in Alzheimer's disease (AD) pathogenesis. In this study, we researched the potential protective effects of resistin against Aβ neurotoxicity in mouse Neuro2a (N2a) cells transfected with the Swedish amyloid precursor protein (Sw-APP) mutant and Presenilin exon 9 deletion mutant (N2a/D9), which overproduced Aβ with abnormal intracellular Aβ accumulation. The results show increased levels of ROS, NO, protein carbonyls, and 4HNE in N2a/D9 cells, which were attenuated by resistin treatment in a dose dependent manner. We also found that resistin could improve mitochondrial function in N2a/D9 cells through increasing the level of ATP and mitochondrial membrane potential. MTT and LDH assay indicated that N2a/D9 cells show increased vulnerability to H2O2-induced insult, which could be ameliorated by resistin. Mechanically, we found that resistin prevented apoptosis signals through reducing the ratio of Bax/Bcl2, the level of cleaved caspase-3, and attenuating cytochrome C release. Finally, the results demonstrated that resistin did not change the production of Aβ1-40 and Aβ1-42 in N2a/D9 cells, which suggests that the protective effects of resistin are independent of APP metabolism. This raises the possibility of novel AD therapies using resistin.
authors.affiliation: The Department of Neurosurgery, Yantai Yu Huang Ding Hospital, Yantai 264000, Shandong, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Nan
authors.initials: N
authors.lastname: Chi
authors.forename: Hongguang
authors.initials: H
authors.lastname: Chen
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Zhang
authors.forename: Yusong
authors.initials: Y
authors.lastname: Bian
authors.forename: Guangqiang
authors.initials: G
authors.lastname: Cui
authors.forename: Chunming
authors.initials: C
authors.lastname: Xiu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000447:Aldehydes; D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D045304:Cytochromes c / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006861:Hydrogen Peroxide / Q000633:toxicity; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects*; D028361:Mitochondrial Diseases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D053764:Presenilin-1 / Q000235:genetics / Q000502:physiology; D050050:Protein Carbonylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D052243:Resistin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000447:Aldehydes; D016229:Amyloid beta-Peptides; D053764:Presenilin-1; D017382:Reactive Oxygen Species; D052243:Resistin; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; C027576:4-hydroxy-2-nonenal
keywords: 2′,7′-dichlorofluorescein-diacetate; 4-HNE; 4-hydroxy-2-nonenal; AD; Alzheimer's disease; Amyloid beta; Apoptosis; Aβ; DCFH-DA; ELISA; LDH; MMP; Mitochondrial dysfunction; NO; Oxidative stress; RNS; ROS; Resistin; amyloid beta; enzyme-linked immunosorbent assay; lactate dehydrogenase; mitochondrial membrane potential; nitric oxide; reactive nitrogen species; reactive oxygen species