Hydrogen peroxide lowers ATP levels in platelets without altering adenyalte energy charge and platelet function.

H Holmsen,L Robkin

doi:10.1016/s0021-9258(17)40614-4

Abstract

H2O2 irreversibly reduced metabolic platelet ATP levels with a corresponding accumulation of hypoxanthine. This process was enhanced by sodium azide or potassium cyanide and by increasing H2O2 concentrations. The adenylate energy charge was unaltered when less than two thirds of the metabolic ATP had disappeared but decreased markedly when more ATP disappeared. Platelet shape change, primary aggregation, dense granule and alpha-granule secretion were unaffected by H2O2-induced lowering of ATP provided that the adenylate energy charge did not fall by more than 5%; at greater adenylate energy charge reduction, platelet functions were inhibited. These results indicate that cell functions depend more on adenyalte energy charge than on the ATP level and expands the applicability of this view from bacterial systems to a mammalian cell, the human platelet.

Highlights

H,O, irreversibly reduced metabolic platelet ATP levels with a corresponding accumulation of hypoxanthine
Primary aggregation, dense granule and a-granule secretion were unaffected by H,O,induced lowering of ATP provided that the adenylate energy charge did not fall by more than 5%; at greater adenylate energy charge reduction, platelet functions were inhibited
The present paper describes the use of hydrogen peroxide as a tool to separate the ATP level and adenylate energy charge in a mammalian system, the human platelet, and shows that like E. coli, platelet function depends more on the adenylate energy charge than on the level of ATP

Summary

Introduction

H,O, irreversibly reduced metabolic platelet ATP levels with a corresponding accumulation of hypoxanthine. The exact ATP-requiring steps for these platelet functions are unknown, but the functions can be separated by their different sensitivities to inhibition of energy metabolism as measured by the parameters of ATP level, adenylate energy charge [2], and probably the ATP turnover rate. The interrelationships of these parameters have not allowed changes in any of the three parameters by the use of inhibitors of energy metabolism without a corresponding change in the others. In the course of an investigation of the inhibitory effects of Health, Education and Welfare Grant 5 PI 7HL 14217

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