s-adenosylhomocysteine and Ischemic-Attack--Transient

Adenosine outflow and adenosine and adenine nucleotide content of hippocampal slices were evaluated under two different experimental conditions: ischemia-like conditions and electrical stimulation (10 Hz). Five minutes of ischemia-like conditions brought about an 8-fold increase in adenosine outflow in the following 5 min during reperfusion, and a 2-fold increase in adenosine content, a 43% decrease in ATP, a 72% increase in AMP and a 30% decrease in energy charge (EC) at the end of the ischemic period. After 10 min of reperfusion ATP, AMP and EC returned to control values, while the adenosine content was further increased. Five minutes of electrical stimulation brought about an 8-fold increase in adenosine outflow that peaked 5 min after the end of stimulation, a 4-fold increase in adenosine content and an 18% decrease in tissue EC at the end of stimulation. After 10 min of rest conditions the adenosine content and EC returned to basal values. The origin of extracellular adenosine from S-adenosylhomocysteine (SAH) was examined under the two different experimental conditions. The SAH hydrolase inhibitor, adenosine-2,3-dialdehyde (10 microM), does not significantly modify the adenosine outflow evoked by electrical stimulation or ischemia-like conditions. This finding excludes a significant contribution by the transmethylation pathway to adenosine extracellular accumulation evoked by an electrical or ischemic stimulus, and confirms that the most likely source of adenosine is from AMP dephosphorylation.

Topics: Adenine Nucleotides; Adenosine; Adenosine Monophosphate; Adenosine Triphosphate; Adenosylhomocysteinase; Animals; Electric Stimulation; Energy Metabolism; Enzyme Inhibitors; Hippocampus; Hydrolases; Ischemic Attack, Transient; Kinetics; Male; Rats; Rats, Wistar; Reperfusion; S-Adenosylhomocysteine

We investigated the effect of S-adenosyl-L-methionine (SAMe) on the prevention of the delayed neuronal death in rats subjected to transient and brief forebrain ischemia. As the results, SAMe dose-dependently protected the hippocampal CA1 neurons from degeneration and necrosis, whose effect was suppressed by simultaneous administration of S-adenosyl-L-homocysteine, a potent inhibitor in transmethylation. No protective effect was observed in CDP-choline, phosphatidylcholine and L-methionine. Therefore, it is necessary for the prevention of the delayed neuronal death to enhance cerebral SAMe level and to activate transmethylation using SAMe as a methyl donor in postischemic brain.

Topics: Animals; Cell Membrane; Cell Survival; Cytidine Diphosphate Choline; Hippocampus; Ischemic Attack, Transient; Male; Methionine; Methylation; Necrosis; Nerve Degeneration; Neurons; Phosphatidylcholines; Rats; Rats, Inbred Strains; S-Adenosylhomocysteine; S-Adenosylmethionine