MAPKs Mediate S Phase Arrest Induced by Vanadate Through a p53-Dependent Pathway in Mouse Epidermal C141 Cells

Details

• Personal Author:
  Chen F ; He H ; Huang C ; Shi X ; Zhang Z
• Description:
  Mitogen-activated protein (MAP) kinases play an important role in mediation of the signal transduction pathway in cellular response to genotoxic stress. Cell growth arrest is considered as an early stage in response to the genotoxic stress. p53 is well-known as a tumor suppression gene involved in both cell growth arrest and apoptosis. The present study investigated the involvement of MAP kinases in vanadate-induced cell growth arrest and the relationship of p53. DNA content analysis showed that vanadate-induced S phase arrest is time- and dose-dependent in p53 wild-type C141 cells but not in p53-deficient C141 cells. Western blotting results indicated that vanadate caused an inactivation of p-cdk2 at Thr160, which is an important kinase for the progression of S phase, and an increase in expression of p21, which is a key for S phase arrest. In p53-deficient cells, vanadate did not induce any observable change in p21 or p-cdk2 level. In addition, vanadate up-regulated phospho-p38 and ERK, two members of MAP kinases. At the same time, vanadate increased the p53 activity as measured by luciferase assay. Addition of PD98059 and SB202190, inhibitors of ERK and p38, respectively, decreased vanadate-induced S phase arrest, reduced p21 levels, restored activation of p-cdk2, and decreased p53 activity. The study demonstrated that vanadate-induced S phase arrest is mediated by both ERK and p38 in a p53-dependent pathway. [Description provided by NIOSH]
• Subjects:
  Occupational Health Safety
• Keywords:
  Cell-growth Cellular-reactions Dose-response Genotoxic-effects In-vitro-study Stress
• 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:
  15
• Issue:
  7
• NIOSHTIC Number:
  nn:20022941
• Citation:
  Chem Res Toxicol 2002 Jul; 15(7):950-956
• Contact Point Address:
  Xianglin Shi, Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Rd., Morgantown, WV 26505
• Email:
  xshi@cdc.gov
• CAS Registry Number:
  Hydroxyl (CAS RN 3352-57-6)
• Federal Fiscal Year:
  2002
• Peer Reviewed:
  True
• Source Full Name:
  Chemical Research in Toxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8a24abd0b62f86d3406066751f3417e63c989f273527222920ef08980b9ddeada5cbe7f4599f1379271d5258cec0e8ad228fb7ffe452d911fc6f8119ee6e6682
• Download URL:
  https://stacks.cdc.gov/view/cdc/199547/cdc_199547_DS1.pdf
• File Type:
  [PDF - 160.06 KB ]