Olfactory Ensheathing Cell-Conditioned Medium Reverts Aβ25-35-Induced Oxidative Damage in SH-SY5Y Cells by Modulating the Mitochondria-Mediated Apoptotic Pathway.
Olfactory ensheathing cells (OECs) are a type of glia from the mammalian olfactory system, with neuroprotective and regenerative properties. β-Amyloid peptides are a major component of the senile plaques characteristic of the Alzheimer brain. The amyloid beta (Aβ) precursor protein is cleaved to amyloid peptides, and Aβ25-35is regarded to be the functional domain of Aβ, responsible for its neurotoxic properties. It has been reported that Aβ25-35triggers reactive oxygen species (ROS)-mediated oxidative damage, altering the structure and function of mitochondria, leading to the activation of the mitochondrial intrinsic apoptotic pathway. Our goal is to investigate the effects of OECs on the toxicity of aggregated Aβ25-35, in human neuroblastoma SH-SY5Y cells. For such purpose, SH-SY5Y cells were incubated with Aβ25-35and OEC-conditioned medium (OECCM). OECCM promoted the cell viability and reduced the apoptosis, and decreased the intracellular ROS and the lipid peroxidation. In the presence of OECCM, mRNA and protein levels of antioxidant enzymes (SOD1 and SOD2) were upregulated. Concomitantly, OECCM decreased mRNA and the protein expression levels of cytochrome c, caspase-9, caspase-3, and Bax in SH-SY5Y cells, and increased mRNA and the protein expression level of Bcl-2. However, OECCM did not alter intracellular Ca2+concentration in SH-SY5Y cells. Taken together, our data suggest that OECCM ameliorates Aβ25-35-induced oxidative damage in neuroblastoma SH-SY5Y cells by inhibiting the mitochondrial intrinsic pathway. These data provide new insights into the functional actions of OECCM on oxidative stress-induced cell damage.
Research Center of Neuroscience, Chongqing Medical University, Chongqing, 400016, China.
Qing-Qing
QQ
Fu
Key Laboratory of Birth Defects and Reproductive Health of the National Health and Family Planning Commission, Chongqing Population and Family Planning Science and Technology Research Institute, Chongqing, 400020, China.
Li
L
Wei
Faculty of Experimental Sciences, Universidad Francisco de Vitoria, Pozuelo de Alarcón, 28223, Madrid, Spain.
Javier
J
Sierra
Research Center of Neuroscience, Chongqing Medical University, Chongqing, 400016, China.
Jian-Zhang
JZ
Cheng
Department of Anatomy, Histology and Neuroscience, Faculty of Medicine, Universidad Autónoma de Madrid, 28029, Madrid, Spain.
María Teresa
MT
Moreno-Flores
Affiliated Hospital of the Academy of Military Medical Sciences, Beijing, 100071, China. youhua307@163.com.
Hua
http://orcid.org/0000-0002-9630-5284
H
You
Research Center of Neuroscience, Chongqing Medical University, Chongqing, 400016, China. huarongyu2003@163.com.
Hua-Rong
HR
Yu
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D016229:Amyloid beta-Peptides; D017077:Culture Media, Conditioned; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C074636:amyloid beta-protein (25-35); D051028:bcl-2-Associated X Protein; D002118:Calcium
Alzheimer’s disease; Apoptosis; Aβ25–35; Mitochondria; Olfactory ensheathing cells; Oxidative damage