1,2,3,4,6-penta-O-galloyl-β-D-glucose protects PC12 Cells from MPP(+)-mediated cell death by inducing heme oxygenase-1 in an ERK- and Akt-dependent manner.
This study examined the ability of 1,2,3,4,6-penta-O-galloyl-β-D-glucose (β-PGG) to induce the expression of heme oxygenase-1 (HO-1) in the PC12 cells and its regulation in the PC12 cells. One week before treatment with the drug, nerve growth factor (NGF) was added to the cultures at a final concentration of 50 ng/mL to induce neuronal differentiation. After drug treatment, HO-1 gene transcription was analyzed by reverse transcription polymerase chain reaction (RT-PCR). Expression of HO-1 and NF-E2-related factor2 (Nrf2) and activation of extracellular signal-regulated kinase (ERK) and Akt were detected by Western blotting. The viability of the PC12 cells treated with different medicines was examined by MTT assay. The oxidative stress in the PC12 cells was evaluated qualitatively and quantitatively by DCFH-DA. The results showed that β-PGG up-regulated HO-1 expression and this increased expression provided neuroprotection against MPP(+)-induced oxidative injury. Moreover, β-PGG induced Nrf2 nuclear translocation, which was found to be upstream of β-PGG-induced HO-1 expression, and the activation of ERK and Akt, a pathway that is involved in β-PGG-induced Nrf2 nuclear translocation, HO-1 expression and neuroprotection. In conclusion, β-PGG up-regulates HO-1 expression by stimulating Nrf2 nuclear translocation in an ERK- and Akt-dependent manner, and HO-1 expression by β-PGG may provide the PC12 cells with an acquired antioxidant defense capacity to survive the oxidative stress.
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Hong
H
Chen
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Hongge
H
Li
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Fei
F
Cao
Department of Obstetrics and Gynecology, Maternal and Child Health Hospital of Fujian Province, Fuzhou, 350001, China.
Lan
L
Zhen
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Jing
J
Bai
Division of Histology and Embryology, Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Shijin
S
Yuan
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. lnlhckao@126.com.
Yuanwu
Y
Mei
D000818:Animals; D016923:Cell Death / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D051547:Heme Oxygenase-1 / Q000235:genetics*; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000235:genetics; D016716:PC12 Cells; D010880:Piperidines / Q000009:adverse effects*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D011720:Pyrazoles / Q000009:adverse effects*; D051381:Rats
C524478:1,3-bis(4-hydroxyphenyl)-4-methyl-5-(4-(2-piperidinylethoxy)phenol)-1H-pyrazole; D047348:Hydrolyzable Tannins; D010880:Piperidines; D011720:Pyrazoles; C435084:pentagalloylglucose; D051547:Heme Oxygenase-1; D051057:Proto-Oncogene Proteins c-akt