Dual effect of pyruvate in isolated nerve terminals: generation of reactive oxygen species and protection of aconitase.
Generation of reactive oxygen species (ROS) in synaptosomes was investigated in the presence of different substrates. When pyruvate was used as a substrate an increased rate of hydrogen peroxide formation was detected by the Amplex Red fluorescent assay, but aconitase, which is known to be a highly sensitive enzyme to ROS was not inhibited. In contrast, pyruvate exerted a partial protection on aconitase against a time-dependent inactivation that occurred when synaptosomes were incubated in the absence of substrates. Disruption of synaptosomal membranes with Triton X-100 prevented the protective effect of pyruvate. It is suggested that citrate and/or isocitrate formed in the metabolism of pyruvate could be responsible for a partial protection of aconitase. Therefore while pyruvate could have a prooxidant effect it could also exert a protective effect on the aconitase.
Tretter
Laszlo
L
Department of Medical Biochemistry, Semmelweis University, Hungarian Academy of Sciences, Szentágothai János Knowledge Center, Budapest, Hungary.
Liktor
Balint
B
Adam-Vizi
Vera
V
D000154:Aconitate Hydratase / Q000378:metabolism*; D000818:Animals; D005947:Glucose / Q000378:metabolism; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism*; D016877:Oxidants / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013574:Synaptosomes / Q000737:chemistry / Q000378:metabolism
D007656:Ketoglutaric Acids; D018696:Neuroprotective Agents; D016877:Oxidants; D017382:Reactive Oxygen Species; D019289:Pyruvic Acid; D006861:Hydrogen Peroxide; D000154:Aconitate Hydratase; D005947:Glucose