Cell surface thiol isomerases may explain the platelet-selective action of S-nitrosoglutathione

Xiao, F. and Gordge, M.P. 2011. Cell surface thiol isomerases may explain the platelet-selective action of S-nitrosoglutathione. Nitric Oxide: Biology and Chemistry. 25 (3), pp. 303-308.

TitleCell surface thiol isomerases may explain the platelet-selective action of S-nitrosoglutathione
AuthorsXiao, F. and Gordge, M.P.
Abstract

S-nitrosoglutathione (GSNO) at low concentration inhibits platelet aggregation without causing vasodilation, suggesting platelet-selective nitric oxide delivery. The mechanism of this selectivity is unknown, but may involve cell surface thiol isomerases, in particular protein disulphide isomerase (csPDI) (EC 5.3.4.1). We have now compared csPDI expression and activity on platelets, endothelial cells and vascular smooth muscle cells, and the dependence on thiol reductase activity of these cell types for NO uptake from GSNO.

csPDI expression was measured by flow cytometry and its reductase activity using the pseudosubstrate dieosin glutathione disulphide. This activity assay was adapted and validated for 96-well plate format. Flow cytometry revealed csPDI on all three cell types, but percentage positivity of expression was higher on platelets than on vascular cells. Consistent with this, thiol isomerase-related reductase activity was higher on platelets (P < 0.01), and cellular activation (with either phorbol myristate acetate or ionomycin) increased csPDI activity on both platelets and smooth muscle cells, but not on endothelium. Intracellular NO delivery from GSNO was greater in platelets than in vascular cells (P < 0.002), and was more sensitive to thiol isomerase inhibition using phenylarsine oxide (P < 0.05).

Increased surface thiol isomerase activity on platelets, compared with cells of the vascular wall, may explain the platelet-selective actions of GSNO and help define its antithrombotic potential.

KeywordsPlatelets; endothelial cells; smooth muscle cells; S-nitrosoglutathione (GSNO); thiol isomerases; protein disulphide isomerase (PDI)
JournalNitric Oxide: Biology and Chemistry
Journal citation25 (3), pp. 303-308
ISSN1089-8603
Year30 Oct 2011
PublisherElsevier
FileXiao_Gordge_final_author_2011.pdf
Digital Object Identifier (DOI)doi:10.1016/j.niox.2011.05.008
Publication dates
Published30 Oct 2011

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