Protein disulfide-isomerase mediates delivery of nitric oxide redox derivatives into platelets
SE Bell, CM Shah, MP Gordge - Biochemical Journal, 2007 - portlandpress.com
SE Bell, CM Shah, MP Gordge
Biochemical Journal, 2007•portlandpress.comS-nitrosothiol compounds are important mediators of NO signalling and can give rise to
various redox derivatives of NO: nitrosonium cation (NO+), nitroxyl anion (NO−) and NO•
radical. Several enzymes and transporters have been implicated in the intracellular delivery
of NO from S-nitrosothiols. In the present study we have investigated the role of GPx
(glutathione peroxidase), the l-AT (l-amino acid transporter) system and PDI (protein
disulfide-isomerase) in the delivery of NO redox derivatives into human platelets. Washed …
various redox derivatives of NO: nitrosonium cation (NO+), nitroxyl anion (NO−) and NO•
radical. Several enzymes and transporters have been implicated in the intracellular delivery
of NO from S-nitrosothiols. In the present study we have investigated the role of GPx
(glutathione peroxidase), the l-AT (l-amino acid transporter) system and PDI (protein
disulfide-isomerase) in the delivery of NO redox derivatives into human platelets. Washed …
S-nitrosothiol compounds are important mediators of NO signalling and can give rise to various redox derivatives of NO: nitrosonium cation (NO+), nitroxyl anion (NO−) and NO• radical. Several enzymes and transporters have been implicated in the intracellular delivery of NO from S-nitrosothiols. In the present study we have investigated the role of GPx (glutathione peroxidase), the L-AT (L-amino acid transporter) system and PDI (protein disulfide-isomerase) in the delivery of NO redox derivatives into human platelets.
Washed human platelets were treated with inhibitors of GPx, L-AT and PDI prior to exposure to donors of NO redox derivatives (S-nitrosoglutathione, Angeli's salt and diethylamine NONOate). Rapid delivery of NO-related signalling into platelets was monitored by cGMP accumulation and DAF-FM (4-amino-5-methylamino-2′7′-difluorofluorescein) fluorescence.
All NO redox donors produced both a cGMP response and DAF-FM fluorescence in target platelets. NO delivery was blocked by inhibition of PDI in a dose-dependent manner. In contrast, inhibition of GPx and L-AT had only a minimal effect on NO-related signalling.
PDI activity is therefore required for the rapid delivery into platelets of NO-related signals from donors of all NO redox derivatives. GPx and the L-AT system appeared to be unimportant in rapid NO signalling by the compounds used in the present study. This does not, however, exclude a possible role during exposure of cells to other S-nitrosothiol compounds, such as S-nitrosocysteine. These results further highlight the importance of PDI in mediating the action of a wide range of NO-related signals.
portlandpress.com