Enhancement of Nuclear Factor-kappaB Activation and Protein Tyrosine Phosphorylation by a Tyrosine Phosphatase Inhibitor, Pervanadate, Involves Reactive Oxygen Species in Silica-Stimulated Macrophages

Details

• Personal Author:
  Castranova, Vincent ; Kang JL ; Lee HS ; Pack IS
• Description:
  Reactive oxygen species (ROS) and phosphorylation events mediated by tyrosine kinase are involved in silica-induced nuclear factor-kappa B (NF-kappaB) activation. Protein tyrosine phosphatase (PTPase) acts to limit protein tyrosine phosphorylation. In the present study, we investigated the role of PTPase in NF-kappaB activation and tyrosine phosphorylation in silica-stimulated macrophages, and the involvement of ROS in these responses. Treatment of mouse peritoneal macrophages (RAW264.7 cells) with a PTPase inhibitor, pervanadate, markedly enhanced the DNA-binding activity of NF-kappaB in the presence or absence of silica. The stimulatory effect of pervanadate on NF-kappaB activation was also demonstrated in LPS-stimulated macrophages. A specific inhibitor of protein tyrosine kinase (PTK), genistein, prevented the NF-kappaB activation induced by pervanadate in the presence of silica while inhibitors of protein kinase A or C, such as staurosporine or H7, had no inhibitory effect on NF-kappaB activation. A variety of antioxidants, such as catalase, superoxide dismutase, N-acetyl cysteine (NAC), and pyrrolidine dithiocarbamate, inhibited NF-kappaB activation induced by pervanadate in the presence of silica. Furthermore, pervanadate markedly enhanced silica- or LPS-induced protein tyrosine phosphorylation in cells. Treatment of macrophages with NAC abolished the increase in tyrosine phosphorylation in cells stimulated with the combination of pervanadate and either silica or LPS or with silica alone. The results suggest that PTPase may play a crucial role in the negative regulation of silica-signaling pathways leading to NF-kappaB activation in macrophages. Furthermore, ROS appear to be involved in downstream signaling between PTPase inhibition and NF-kappaB activation. [Description provided by NIOSH]
• Subjects:
  Aluminum Silicates Animals Antioxidants Blood Laboratories Macrophages Nervous System Nervous System Diseases Nervous System Disorders Occupational Health Safety Silicon Dioxide

  More +
• Keywords:
  Animal-studies Antioxidation Author Keywords: NF-kB Brain-damage Cell-damage Central-nervous-system Central-nervous-system-disorders Laboratory-animals Laboratory-testing Neurotoxic-effects Neurotoxicity Neurotoxicology Pervanadate Proteins Reactive Oxygen Species Silica-dusts Silicates

  More +
• ISSN:
  0300-483X
• 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
• Pages in Document:
  81-89
• Volume:
  151
• Issue:
  1
• NIOSHTIC Number:
  nn:20025229
• Citation:
  Toxicology 2000 Oct; 151(1-3):81-89
• Contact Point Address:
  Department of Physiology, Division of Cell Biology, College of Medicine, Ewha Medical Research Center and Center for Cell Signaling Research, Ewha Womans University, 911-1 Mok-6-dong, Yangcheon-ku, 158-056, Seoul, South Korea
• Email:
  jihee@mm.ewha.ac.kr
• CAS Registry Number:
  L-Tyrosine (CAS RN 55520-40-6)
• Federal Fiscal Year:
  2001
• Peer Reviewed:
  True
• Source Full Name:
  Toxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:b4335c3873dd8a66660fd61aa218f00f0d261b0c16dbfe9c52d39879478d365a04eacf47d578698f6d4661fab88e8daf46a1fe9576f136a97470407499789a81
• Download URL:
  https://stacks.cdc.gov/view/cdc/196695/cdc_196695_DS1.pdf
• File Type:
  [PDF - 292.69 KB ]