Thrombin or Ca(++)-ionophore-mediated fall in endothelial ATP levels independent of poly(ADP-Ribose) polymerase activity and NAD levels--comparison with the effects of hydrogen peroxide.

• Published in: Nucleosides, Nucleotides and Nucleic Acids
• Main Authors: Halldórsson, Haraldur, Thors, Brynhildur, Thorgeirsson, Gudmundur
• Other Authors: 1 Univ Iceland, Pharmacol, Fac Med, IS-101 Reykjavik, Iceland 2 Univ Iceland, Dept Med, Fac Med, Landspitali Univ Hosp, IS-101 Reykjavik, Iceland
• Format: Article in Journal/Newspaper
• Language: English
• Published: Taylor & Francis 2015
• Subjects: Poly(ADP-ribose) Polymerases/metabolism*; Endothelium; Thrombin; Iceland
• Online Access: http://hdl.handle.net/2336/566205; https://doi.org/10.1080/15257770.2014.984072

To access publisher's full text version of this article click on the hyperlink at the bottom of the page To test the hypothesis that a fall in cellular ATP following stimulation of endothelial cells with thrombin is secondary to a decrease in NAD levels caused by poly(ADP-Ribose)polymerase (PARP), we measured the levels of NAD and ATP in endothelial cells after treatment with thrombin, the Ca(++)-ionophore A23187, or hydrogen peroxide (H2O2), and compared the effects of inhibitors of PARP, NAD synthesis, and ADP-ribose breakdown on these responses. Neither thrombin nor A23187 caused a reduction in endothelial NAD levels and A23187 affected ATP levels independently of NAD levels or PARP activity. H2O2 induced lowering of NAD caused modest lowering of ATP but marked additional ATP-lowering, independent of PARP and NAD, was also demonstrated. We conclude that in endothelial cells ATP levels are largely independent of NAD and PARP, which do not play a role in thrombin or Ca(++)-ionophore-mediated lowering of ATP. H2O2 caused ATP lowering through a similar mechanism as thrombin and A23187 but, additionally, caused a further ATP lowering through its intense stimulation of PARP and marked lowering of NAD. University of Iceland Research Fund Research Fund of Landspitali, University Hospital Helga Jonsdottir and Sigurlidi Kristjansson Memorial fund