title: Curcumin inhibits appoptosin-induced apoptosis via upregulating heme oxygenase-1 expression in SH-SY5Y cells.
abstract: OBJECTIVE
  Appoptosin (SLC25A38) is a pro-apoptotic protein, which is upregulated in Alzheimer's disease (AD) brains and plays an important role in promoting the pathological progress of AD. The aim of this study was to investigate the effects of curcumin from the rhizome of Curcuma longa on appoptosin-induced apoptosis in SH-SY5Y cells.
  
  
  METHODS
  SH-SY5Y cells were pretreated with curcumin, then transfected with appoptosin or vector. The apoptotic cells were detected with Annexin V staining analysis by flow cytometry. The expression of cleaved caspase-3, appoptosin, heme oxygenase-1 (HO-1) was examined using Western blotting. Intracellular level of ROS was measured with DCFH-DA staining by flow cytometry analysis. Mitochondrial membrane potential (ΔΨm) was detected with JC-1 staining under a fluorescence microscope and quantified by fluorescence ratio detection.Overexpression of appoptosin in SH-SY5Y cells markedly increased cell apoptosis accompanied by reduced HO-1 expression, increased intracellular heme level, ROS overproduction and ΔΨm impairment. Treatment of SH-SY5Y cells with curcumin (2.5-20 μmol/L) for 24 h did not significantly affect their viability. However, pretreatment with curcumin (2.5-20 μmol/L) dose-dependently attenuated all above-mentioned pathological changes in appoptosin-transfected SH-SY5Y cells.
  
  
  RESULTS
  Overexpression of appoptosin in SH-SY5Y cells markedly increased cell apoptosis accompanied by reduced HO-1 expression, increased intracellular heme level, ROS overproduction and ΔΨm impairment. Treatment of SH-SY5Y cells with curcumin (2.5-20 μmol/L) for 24 h did not significantly affect their viability. However, pretreatment with curcumin (2.5-20 μmol/L) dose-dependently attenuated all above-mentioned pathological changes in appoptosin-transfected SH-SY5Y cells.
  
  
  CONCLUSIONS
  Curcumin inhibits appoptosin-induced apoptosis in SH-SY5Y cells by upregulating the expression of HO-1, reducing the production of intracellular heme and ROS, and preventing the ΔΨm loss.
authors.affiliation: Department of Neurology, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou 350001, China.
authors.forename: Kun-mu
authors.initials: KM
authors.lastname: Zheng
authors.affiliation: 1] Department of Neurology, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou 350001, China [2] Key Laboratory of Brain Aging and Neurodegenerative Disease, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou 350001, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research and Institute of Neuroscience, College of Medicine, Xiamen University, Xiamen 361005, China.
authors.forename: Cui-lin
authors.initials: CL
authors.lastname: Zhang
authors.affiliation: Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research and Institute of Neuroscience, College of Medicine, Xiamen University, Xiamen 361005, China.
authors.forename: Yun-wu
authors.initials: YW
authors.lastname: Zhang
authors.affiliation: 1] Department of Neurology, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou 350001, China [2] Key Laboratory of Brain Aging and Neurodegenerative Disease, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou 350001, China.
authors.forename: Xiao-chun
authors.initials: XC
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; D033681:Mitochondrial Membrane Transport Proteins; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D003474:Curcumin