Reactive Oxygen Species-Activated Akt/ASK1/p38 Signaling Pathway in Nickel Compound-Induced Apoptosis in BEAS 2B Cells

Details

• Personal Author:
  Bi YY ; Chang QS ; Chen F ; Chen G ; Luo J ; Pan JJ ; Shi XL ; Son Y ; Wang X ; Zhang Z
• Description:
  Nickel compounds are carcinogenic to humans, possibly through induction of reactive oxygen species (ROS) that damage macromolecules including DNA and proteins. The aim of the present study is to elucidate the role of the ROS-mediated Akt/apoptosis-regulating signal kinase (ASK) 1/p38 pathway in nickel-induced apoptosis. Exposure of human bronchial epithelial cells (BEAS-2B) to nickel compounds induced the generation of ROS and activation of Akt that is associated with the activation of ASK1 and p38 mitogen-activated protein kinase. Immunoblotting suggested a down-regulation of several antiapoptotic proteins, including Bcl-2 and Bcl-xL in the nickel compound-treated cells. Indeed, a notable cell apoptosis following nickel compound treatment is evident as revealed by flow cytometry analysis. N-Acetyl-L-cysteine (NAC, a general antioxidant) and vitamin E or catalase (a specific H2O2 inhibitor) all decreased nickel-induced ROS generation. Scavenging of nickel-induced ROS by NAC or catalase attenuated Akt, ASK1, and p38 MAPK activation and apoptosis, which implies involvement of ROS in the Akt/ASK1/p38 pathway. In addition, nickel-induced activation of p38 MAPK was attenuated by a small interference of RNA specific to ASK1 (siRNA ASK1), implying that p38 MAPK was downstream of ASK1, while ASK1 activation was not reversely regulated by the inhibition of p38 MAPK by SB203580, a widely used p38 MAPK inhibitor. Silencing Akt by siRNA reduced the activation of ASK I and p38 MAPK and cell apoptosis, whereas without nickel stimulation, siRNA Akt had no effect on the activation of ASK1 and p38 MAPK. Thus, these results suggest that the ROS-dependent Akt-ASK1-p38 axis is important for nickel-induced apoptosis. [Description provided by NIOSH]
• Subjects:
  Carcinogens Chemistry Cytotoxins Environmental Monitoring Hazardous Substances Hypersensitivity Irritants Occupational Health Oxidants Respiratory Hypersensitivity Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Carcinogenesis Cell-biology Cell-metabolism Cellular-reactions Chemical-analysis Chemical-composition Chemical-hypersensitivity Chemical-reactions Cytotoxic-effects Exposure-assessment Exposure-levels Exposure-limits Inhalation-studies Oxidative-metabolism Oxidative-processes Pulmonary-system-disorders Respiratory-hypersensitivity Respiratory-irritants Toxic-effects Toxic-materials

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• ISSN:
  0893-228X
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; 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:
  23
• Issue:
  3
• NIOSHTIC Number:
  nn:20036577
• Citation:
  Chem Res Toxicol 2010 Mar; 23(3):568-577
• Contact Point Address:
  Xianglin Shi, Graduate Center for Toxicology and Department of Medicine, University of Kentucky, 234 Health Science Research Building, Lexington, Kentucky 40536
• Email:
  xshi5@email.uky.edu
• CAS Registry Number:
  Nickel (CAS RN 7440-02-0)
• Federal Fiscal Year:
  2010
• NORA Priority Area:
  Manufacturing ; Mining
• Peer Reviewed:
  True
• Source Full Name:
  Chemical Research in Toxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e46de52ca85a27593770e49c0a0ad6cd78b896dbcfea48ed5ca78c0c62a4188bf1ae7b0054d36d5e4fb7451d83c0291d7360223f759004c3a6e6d724c11f034d
• Download URL:
  https://stacks.cdc.gov/view/cdc/187943/cdc_187943_DS1.pdf
• File Type:
  [PDF - 2.68 MB ]