Curcumin protected PC12 cells against beta-amyloid-induced toxicity through the inhibition of oxidative damage and tau hyperphosphorylation.
One of the pathological hallmarks of Alzheimer's disease is the progressive accumulation of beta-amyloid (Abeta) in the form of senile plaques, and Abeta insult to neuronal cells has been identified as one of the major causes of the onset of the disease. Curcumin, the major and most active antioxidant of Curcuma longa, protects neuronal cells against Abeta-induced toxicity. Therefore, in this study, we investigated the neuroprotective mechanisms by which curcumin acts against Abeta (25-35)-induced toxicity in PC12 cells. Following the exposure of PC12 cells to 10 microM Abeta (25-35) for 24h, significant increases in the level of antioxidant enzymes, and DNA damage were observed, and these increases were accompanied by a decrease in cell viability, and an increase in intracellular calcium levels and tau hyperphosphorylation. In addition, pretreatment of PC12 cells with 10 microg/ml curcumin for 1h significantly reversed the effect of Abeta, by decreasing the oxidative stress, and DNA damage induced by Abeta, as well as attenuating the elevation of intracellular calcium levels and tau hyperphosphorylation induced by Abeta. Taken together, these data indicate that curucmin protected PC12 cells against Abeta-induced neurotoxicity through the inhibition of oxidative damage, intracellular calcium influx, and tau hyperphosphorylation.
Environmental Toxico-Genomic and Proteomic Center, College of Medicine, Korea University, Anamdong 5, Sungbuk ku, Seoul 136-705, Republic of Korea.
So-Young
SY
Park
Hyo-Shin
HS
Kim
Eun-Kyung
EK
Cho
Bo-Youn
BY
Kwon
Sohee
S
Phark
Kwang-Woo
KW
Hwang
Donggeun
D
Sul
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D001713:Biphenyl Compounds; D002118:Calcium / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D020552:Comet Assay; D003474:Curcumin / Q000494:pharmacology*; D004249:DNA Damage; D004591:Electrophoresis, Polyacrylamide Gel; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D010851:Picrates / Q000378:metabolism; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D001713:Biphenyl Compounds; D010851:Picrates; D016875:tau Proteins; C004931:1,1-diphenyl-2-picrylhydrazyl; D002374:Catalase; D013482:Superoxide Dismutase; D003474:Curcumin; D002118:Calcium