Nitrosative Stress Induces Phosphatidylserine Externalization: Signaling Role in Phagocytes

Details

• Personal Author:
  Bayir H ; Cai P ; Fadeel B ; Kagan VE ; Konduru NV ; Potapovich A ; Shvedova AA ; Stoyanovsky D ; Tyurin VA ; Tyurina YY
• Description:
  Aminophospholipid translocase (APT) is responsible for asymmetric distribution of phosphatidylserine (PS) across plasma membrane. The enzyme contains catalytically competent cysteines whose oxidation/alkylation results in loss of its activity. Because protein S-nitrosylation can act as a regulatory redox-sensitive mechanism, we hypothesized that nitrosative stress enhances PS externalization in cells by inhibiting APT activity. This pathway should be particularly important during inflammation whereby oxidative/nitrosative burst generated by macrophages may cause direct nitrosylation or trans-nitrosylation of APT in target cells. To experimentally address this hypothesis we utilized HL-60 cells that express high activity of APT. S-nitroso-L-cysteine-ethyl ester (SNCEE) and S-nitroso-glutathione (GSNO) were used as prototypical cell-permeable and cell impermeable trans-nitrosylating reagents. HL-60 cells externalized PS in response to SNCEE or GSNO treatment (50-100 uM, 0.5h at 37 C) as evidenced by annexin V binding assay and fluorescence microscopy. No cytotoxic effects were induced by either of the trans-nitrosating agents. RAW 264.7 macrophages elicited enhanced phagocytizing activity towards "nitrosylated" HL-60 cells. We speculate that our proposed mechanism of macrophage induced nitrosative stress contributes to effective clearance of apoptotic cells and regulates switching of acute inflammatory response to anti-inflammatory phase as has been observed in the lung and in the brain in in vivo experiments with inhalation of single-walled carbon nanotubes and cortical trauma, respectively. [Description provided by NIOSH]
• Subjects:
  Animals Enzymes Laboratories Lung Occupational Health Respiratory System Safety
• Keywords:
  Animal-studies In-vivo-studies Laboratory-animals Microscopy Nanotechnology Phagocytes
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; Pennsylvania ; 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:
  90
• Issue:
  1
• NIOSHTIC Number:
  nn:20029895
• Citation:
  Toxicologist 2006 Mar; 90(1):237
• Federal Fiscal Year:
  2006
• NORA Priority Area:
  Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 45th Annual Meeting and ToxExpo, March 5-9, 2006, San Diego, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:bb3c298f439903634e327f7b8c3bb4dd76b1c5ce803393b46b200c09afd010d98ef94de0d12667463b785452ddd44a6cca02606f75251aaf631abd532a6a175f
• Download URL:
  https://stacks.cdc.gov/view/cdc/190788/cdc_190788_DS1.pdf
• File Type:
  [PDF - 152.37 KB ]