PMID- 28122344
OWN - NLM
STAT- MEDLINE
DCOM- 20170818
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 9
DP  - 2017 Feb 28
TI  - Cytoprotective effect of chlorogenic acid against hydrogen peroxide-induced 
      oxidative stress in MC3T3-E1 cells through PI3K/Akt-mediated Nrf2/HO-1 signaling 
      pathway.
PG  - 14680-14692
LID - 10.18632/oncotarget.14747 [doi]
AB  - Osteoporosis is a disorder of bone and its development is closely associated with 
      oxidative stress and reactive oxygen species (ROS). Chlorogenic acid (CGA) has 
      potential antioxidant effects and its pharmacological action in osteoblasts is 
      not clearly understood. The present study aimed to clarify the protective effects 
      and mechanisms of CGA on hydrogen peroxide (H2O2)-induced oxidative stress in 
      osteoblast cells. MC3T3-E1 cells were treated with H2O2 to induce oxidative 
      stress model in vitro. Cells were treated with CGA prior to H2O2 exposure, the 
      intracellular ROS production, malondialdehyde content, nitric oxide release and 
      glutathione level were measured. We also investigated the protein levels of heme 
      oxygenase-1 (HO-1), the nuclear translocation of transcription factor 
      NF-erythroid 2-related factor (Nrf2) and the phosphorylation levels of Akt in 
      CGA-treated cells. The results showed that pretreatment of CGA could reverse the 
      inhibition of cell viability and suppress the induced apoptosis and caspase-3 
      activity. Additionally, it significantly reduced H2O2-induced oxidative damage in 
      a dose-dependent manner. Furthermore, it induced the protein expression of HO-1 
      together with its upstream mediator Nrf2, and activated the phosphorylation of 
      Akt in MC3T3-E1 cells. LY294002, a PI3K/Akt inhibitor, significantly suppressed 
      the CGA-induced Nrf2 nuclear translocation and HO-1 expression. Reduction of cell 
      death mediated by CGA in presence of H2O2 was significantly inhibited by Zinc 
      protoporphyrin IX (a HO-1 inhibitor) and LY294002. These data demonstrated that 
      CGA protected MC3T3-E1 cells against oxidative damage via PI3K/Akt-mediated 
      activation of Nrf2/HO-1 pathway, which may be an effective drug in treatment of 
      osteoporosis.
FAU - Han, Dandan
AU  - Han D
AD  - College of Veterinary Medicine, China Agricultural University, Beijing 100193, P. 
      R. China.
FAU - Chen, Wei
AU  - Chen W
AD  - College of Veterinary Medicine, China Agricultural University, Beijing 100193, P. 
      R. China.
FAU - Gu, Xiaolong
AU  - Gu X
AD  - College of Veterinary Medicine, China Agricultural University, Beijing 100193, P. 
      R. China.
FAU - Shan, Ruixue
AU  - Shan R
AD  - College of Veterinary Medicine, China Agricultural University, Beijing 100193, P. 
      R. China.
FAU - Zou, Jiaqi
AU  - Zou J
AD  - College of Veterinary Medicine, China Agricultural University, Beijing 100193, P. 
      R. China.
FAU - Liu, Gang
AU  - Liu G
AD  - College of Veterinary Medicine, China Agricultural University, Beijing 100193, P. 
      R. China.
FAU - Shahid, Muhammad
AU  - Shahid M
AD  - College of Veterinary Medicine, China Agricultural University, Beijing 100193, P. 
      R. China.
FAU - Gao, Jian
AU  - Gao J
AD  - College of Veterinary Medicine, China Agricultural University, Beijing 100193, P. 
      R. China.
FAU - Han, Bo
AU  - Han B
AD  - College of Veterinary Medicine, China Agricultural University, Beijing 100193, P. 
      R. China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Membrane Proteins)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, mouse)
RN  - 0 (Oxidants)
RN  - 0 (Reactive Oxygen Species)
RN  - 318ADP12RI (Chlorogenic Acid)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 1.14.14.18 (Hmox1 protein, mouse)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Blotting, Western
MH  - Caspase 3/metabolism
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Chlorogenic Acid/*pharmacology
MH  - Cytoprotection/drug effects
MH  - Heme Oxygenase-1/*metabolism
MH  - Hydrogen Peroxide/*pharmacology
MH  - Membrane Proteins/*metabolism
MH  - Mice
MH  - NF-E2-Related Factor 2/*metabolism
MH  - Osteoblasts/cytology/drug effects/metabolism
MH  - Oxidants/pharmacology
MH  - Oxidative Stress/*drug effects
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/drug effects
PMC - PMC5362435
OTO - NOTNLM
OT  - MC3T3-E1 cells
OT  - Nrf2/HO-1 pathway
OT  - chlorogenic acid
OT  - cytoprotection
OT  - oxidative stress
COIS- CONFLICTS OF INTEREST The author declares that there is no conflict of interest 
      regarding the publication of this paper.
EDAT- 2017/01/26 06:00
MHDA- 2017/08/19 06:00
PMCR- 2017/02/28
CRDT- 2017/01/26 06:00
PHST- 2016/11/22 00:00 [received]
PHST- 2017/01/11 00:00 [accepted]
PHST- 2017/01/26 06:00 [pubmed]
PHST- 2017/08/19 06:00 [medline]
PHST- 2017/01/26 06:00 [entrez]
PHST- 2017/02/28 00:00 [pmc-release]
AID - 14747 [pii]
AID - 10.18632/oncotarget.14747 [doi]
PST - ppublish
SO  - Oncotarget. 2017 Feb 28;8(9):14680-14692. doi: 10.18632/oncotarget.14747.