Regulation of apoptosis by Bcl-2 cysteine oxidation in human lung epithelial cells

Details

• Personal Author:
  Callery PS ; Chanvorachote P ; Luanpitpong S ; Rojanasakul Y ; Stehlik C ; Tse W ; Wang L
• Description:
  Hydrogen peroxide is a key mediator of oxidative stress known to be important in various cellular processes, including apoptosis. B-cell lymphoma-2 (Bcl-2) is an oxidative stress-responsive protein and a key regulator of apoptosis; however, the underlying mechanisms of oxidative regulation of Bcl-2 are not well understood. The present study investigates the direct effect of H2O2 on Bcl-2 cysteine oxidation as a potential mechanism of apoptosis regulation. Exposure of human lung epithelial cells to H2O2 induces apoptosis concomitant with cysteine oxidation and down-regulation of Bcl-2. Inhibition of Bcl-2 oxidation by antioxidants or by site-directed mutagenesis of Bcl-2 at Cys-158 and Cys-229 abrogates the effects of H2O2 on Bcl-2 and apoptosis. Immunoprecipitation and confocal microscopic studies show that Bcl-2 interacts with mitogen-activated protein kinase (extracellular signal-regulated kinase 1/2 [ERK1/2]) to suppress apoptosis and that this interaction is modulated by cysteine oxidation of Bcl-2. The H2O2-induced Bcl-2 cysteine oxidation interferes with Bcl-2 and ERK1/2 interaction. Mutation of the cysteine residues inhibits the disruption of Bcl-2-ERK complex, as well as the induction of apoptosis by H2O2. Taken together, these results demonstrate the critical role of Bcl-2 cysteine oxidation in the regulation of apoptosis through ERK signaling. This new finding reveals crucial redox regulatory mechanisms that control the antiapoptotic function of Bcl-2. [Description provided by NIOSH]
• Subjects:
  Antioxidants Cytology Energy Metabolism Lung Microbiology Mutagens Occupational Health Respiratory System Safety Spectrum Analysis
• Keywords:
  Cell-alteration Cell-damage Cellular-function Drug-interaction Humans Hydroxides Lung-cells Metabolism Microscopic-analysis Mutagenesis Oxidation-reduction-reactions Oxidative-processes Oxides Pharmacodynamics Proteins Spectrographic-analysis

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• ISSN:
  1059-1524
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Illinois ; OSHA Region 3 ; OSHA Region 5 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  24
• Issue:
  6
• NIOSHTIC Number:
  nn:20042958
• Citation:
  Mol Biol Cell 2013 Mar; 24(6):858-869
• Contact Point Address:
  Yon Rojanasakul, Department of Basic Pharmaceutical Sciences and Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506
• Email:
  yrojan@hsc.wvu.edu
• CAS Registry Number:
  3-Sulfenoalanine (CAS RN 5722-80-5) ; Doxorubicin (CAS RN 23214-92-8) ; Hydrogen peroxide (CAS RN 7722-84-1)
• Federal Fiscal Year:
  2013
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Molecular Biology of the Cell
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:af16adf02ce8afd9ae7892617a9d4ff4032ec804b154c39d0f84d620d003cd94d8b7bd94bdf8e25d567018d01610da2226390bff1af00e3fb5351a02dc97141a
• Download URL:
  https://stacks.cdc.gov/view/cdc/195007/cdc_195007_DS1.pdf
• File Type:
  [PDF - 7.19 MB ]