Glucose and pyruvate regulate cytokine-induced nitric oxide
production by cardiac myocytes.
Finkel, Carmine V. Oddis Mitchell S.
Departments of Pathology, Surgery, Medicine and Pharmacology,
University of Pittsburgh School of Medicine, Pittsburgh, PA 15213
APStracts 3:0180C, 1996.
Metabolic requirements for the production of nitric oxide (NO) by
cytokine-stimulated neonatal rat cardiac myocytes (CM) were studied.
CM were cultured for 48 hrs in media containing interleukin 1-[beta]
(IL-1) and free fatty acids. Removal of glucose from the media
partially inhibited IL-1 stimulated nitrite (NO2-) production (8.1+/
-0.3 vs. 4.4+/-0.6nmol/ 1.25x105cells/48hrs p<.01;n=12). The
glycolytic inhibitor, 2-deoxyglucose (2DG), completely inhibited IL-1
stimulated NO2- production (0.7+/-0.5nmol/1.25x105cells/48hrs;
p<.01;n=12). The addition of the glycolytic end product,
pyruvate (Py), completely blocked the 2DG inhibition of IL-1
stimulated NO2- production (7.4+/-0.4nmol/1.25x105cells/
48hrs;p<.01;n=12). Py alone did not significantly enhance NO2-
production in the presence or absence of glucose (p=ns;n=12). The
inactive analogue, 3-0-methylglucose had no effect on NO2- production
(p=ns;n=12). RT-PCR revealed that Py blocked 2DG inhibition of
inducible NO synthase mRNA expression. Neither 2DG nor Py had any
effect on GTP-cyclohydrolase I mRNA expression in CM. We report for
the first time that optimal IL-1 stimulated NO production by CM
requires both glucose and the glycolytic end product, pyruvate.
Received 30 November 1995; accepted in final form 27 May 1996.
APS Manuscript Number C714-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 17 June 96