title: Cytoprotective effect of chlorogenic acid against hydrogen peroxide-induced oxidative stress in MC3T3-E1 cells through PI3K/Akt-mediated Nrf2/HO-1 signaling pathway.
abstract: 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.
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing 100193, P. R. China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Han
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing 100193, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing 100193, P. R. China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Gu
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing 100193, P. R. China.
authors.forename: Ruixue
authors.initials: R
authors.lastname: Shan
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing 100193, P. R. China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Zou
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing 100193, P. R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing 100193, P. R. China.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Shahid
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing 100193, P. R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing 100193, P. R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Han
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002726:Chlorogenic Acid / Q000494:pharmacology*; D019610:Cytoprotection / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D016877:Oxidants; D017382:Reactive Oxygen Species; D002726:Chlorogenic Acid; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3
keywords: MC3T3-E1 cells; Nrf2/HO-1 pathway; chlorogenic acid; cytoprotection; oxidative stress