Protective effect of pyrroloquinoline quinone against Abeta-induced neurotoxicity in human neuroblastoma SH-SY5Y cells.
The neurotoxicity of aggregated beta-amyloid (Abeta) has been implicated as a critical cause in the pathogenesis of Alzheimer's disease (AD). It can cause neurotoxicity in AD by evoking a cascade of oxidative damage-dependent apoptosis to neurons. In the present study, we for the first time investigated the protective effect of pyrroloquinoline quinone (PQQ), an anionic, water soluble compound that acts as a redox cofactor of bacterial dehydrogenases, on Abeta-induced SH-SY5Y cytotoxicity. Abeta(25-35) significantly reduced cell viability, increased the number of apoptotic-like cells, and increased ROS production. All of these phenotypes induced by Abeta(25-35) were markedly reversed by PQQ. PQQ pretreatment recovered cells from Abeta(25-35)-induced cell death, prevented Abeta(25-35)-induced apoptosis, and decreased ROS production. PQQ strikingly decreased Bax/Bcl-2 ratio, and suppressed the cleavage of caspase-3. These results indicated that PQQ could protect SH-SY5Y cells against beta-amyloid induced neurotoxicity.
Zhang
Jun-Jing
JJ
Department of Surgery, The Affiliated Hospital of Inner Mongolia Medical College, 1 Tongdao Beijie, Hohhot, 010050, China. zhangxiaofei1998@yahoo.com.cn
Zhang
Rui-Fang
RF
Meng
Xing-Kai
XK
D016229:Amyloid beta-Peptides / Q000502:physiology* / Q000633:toxicity; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D045542:PQQ Cofactor / Q000494:pharmacology*; D010446:Peptide Fragments / Q000502:physiology* / Q000633:toxicity; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C074636:amyloid beta-protein (25-35); D045542:PQQ Cofactor; D053148:Caspase 3