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We have previously reported that GDP‐bound αβγ‐trimeric GTP‐binding (G) proteins can be converted into the active GTP‐bound form with nucleoside diphosphate (NDP) kinase and ATP, although its exact activation mechanism still remains to be resolved. In the present study, we investigated whether NDP kinase activity was modified by mastoparan, a wasp venom peptide that is known to activate G proteins as an agonist‐receptor complex. The activity of NDP kinase measured by the formation of GTP from ATP and GDP was markedly stimulated, when the kinase was incubated with mastoparan. The concentration of mastoparan required for the activation was much lower than that observed for the peptidc‐induced activation of G proteins under similar assay conditions. There was also an increase in the phosphorylated intermediate of NDP kinase as well as the catalytic activity upon its incubation with mastoparan. These results suggest that mastoparan not only activates G proteins directly via guanine nucleotide exchange reaction but also stimulates NDP kinase activity.

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Alzheimer's disease (AD) is among the most common causes of progressive cognitive impairment in humans and is characterized by neurodegeneration in the brain. Lipid peroxidation is thought to play a role in the pathogenesis of AD. 4-hydroxynonenal (HNE) results from peroxidation of polyunsaturated fatty acids and it in turn gives evidence of lipid peroxidation in vivo. HNE reacts with protein histidine residue to form a stable HNE-histidine Michael adduct. To clarify the influence of lipid peroxidation on the pathogenesis of AD, we measured HNE-histidine Michael adduct in hippocampi from four AD patients and four age-matched controls by means of semiquantitative immunohistochemistry using a specific antibody to cyclic hemiacetal type of HNE-histidine Michael adduct. This antibody does not react with the ring-opened form of HNE-histidine Michael adduct and the pyrrole form of HNE-lysine Michael adduct. The HNE adduct was detected in the hippocampi of both AD and control donors, especially in the CA2, CA3 and CA4 sectors. Immunoreactive intensity of HNE adduct in these sectors were significantly higher in AD patients than in the controls. The HNE adduct was found in the perikarya of pyramidal cells in the hippocampus. These results show that the hippocampi of patients with AD undergo lipid peroxidation and imply that this activity underlies the production of cytotoxic products such as HNE that are responsible for the pathogenesis of AD.The progressive cognitive impairment of Alzheimer's disease (AD) is associated with neuronal loss as well as the formation of neurofibrillary tangles (NFTs) and senile plaques in the brain (25). Free radical-mediated oxidative damage, energy depletion, deposition of amyloids and NFTs, excitotoxicity, and vascular endothelial cell damage are all thought to participate in the pathogenesis of AD (13). Oxygen-derived free radicals, byproducts of respiration, cause oxidative damage to cellular biomolecules including lipids, proteins and nucleic acids. The brain seems to be especially vulnerable to lipid peroxidation by free radicals, because it consumes approximately one-fifth of humans' oxygen intake, has a relative paucity of antioxidant systems and contains high concentrations of polyunsaturated fatty acids (PUFAs) (11). Lipid peroxidation results in structural damage to membranes and generation of secondary products such as reactive aldehydes