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S-nitrosylation of aminophospholipid translocase: A new signaling role in apoptosis and phagocytosis.

Authors
Tyurina-YY; Tyurin-VA; Konduru-NV; Basova-L; Potapovich-AI; Bayir-H; Stoyanovsky-D; Fadeel-B; Shvedova-AA; Kagan-VE
Source
Biochim Biophys Acta Bioenerg 2006 May-Jun; 1757(5-6)(Suppl 1):105
NIOSHTIC No.
20031256
Abstract
Plasma membrane aminophospholipid translocase (APT) is mainly responsible for asymmetric distribution of phosphatidylserine (PS) on cell surface. The enzyme can be S-nitrosylated resulting in the loss of its activity. Therefore, we hypothesized that nitrosative stress - acting through APT Snitrosylation - 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. Snitroso- 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 as evidenced by annexin V binding assay and fluorescence microscopy. No cytotoxic effects were induced by either of the transnitrosating agents. RAW 264.7 macrophages elicited enhanced phagocytizing activity towards "nitrosylated" HL-60 cells. Assessments of APT activity revealed that S-nitrosaylation is indeed associated with the changed activity of the enzyme. We speculate that macrophage induced nitrosative stress contributes to effective clearance of apoptotic cells. Consequently, nitrosative stress is involved in regulation of acute inflammatory response and its switch 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.
Keywords
Amino-compounds; Enzymes; Cell-cultures; Cell-wall-permeability; Microscopy; Cytotoxins; Cytotoxicity; Cytotoxic-effects; Phagocytes; Nanotechnology
Publication Date
20060501
Document Type
Journal Article
Email Address
vkagan@eoh.pitt.edu
Funding Type
Grant
Fiscal Year
2006
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-008282
Issue of Publication
5-6
ISSN
0005-2728
NIOSH Division
HELD
Priority Area
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
Source Name
Biochimica et Biophysica Acta - Bioenergetics
State
WV; PA
Performing Organization
University of Pittsburgh at Pittsburgh
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