Journal
NEUROCHEMICAL RESEARCH
Volume 27, Issue 12, Pages 1593-1598Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1023/A:1021670607647
Keywords
homocystinuria; hyperhomocysteinemia; homocysteine; Na+,K+-ATPase
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Hyperhomocysteinemia occurs in homocystinuria, an inherited metabolic disease clinically characterized by thromboembolic episodes and a variable degree of neurological dysfunction whose pathophysiology is poorly known. In this study, we induced elevated levels of homocysteine (Hcy) in blood ( 500 muM), comparable to those of human homocystinuria, and in brain ( 60 nmol/g wet tissue) of young rats by injecting subcutaneously homocysteine (0.3-0.6 mumol/g of body weight) twice a day at 8-hr intervals from the 6th to the 28th postpartum day. Controls received saline in the same volumes. Na+, K+-ATPase and Mg2+-ATPase activities were determined in the hippocampus of treated Hcy- and saline-treated rats. Chronic administration of Hcy significantly decreased (40%) Na+, K+-ATPase activity but did not alter Mg2+-ATPase activity. Considering that Na+, K+-ATPase plays a crucial role in the central nervous system, our results suggest that the brain dysfunction found in homocystinuria may be related to the reduction of brain Na+, K+-ATPase activity.
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