Contribution of Lipid Dynamics on the Inhibition of Bovine Brain Synaptosomal Na^+-K^+-ATPase Activity Induced by 4-Hydroxy-2-nonenal
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概要
- 論文の詳細を見る
The effects of lipid hydroperoxide degradation products, such as 4-hydroxy-2-nonenal (HNE) and malondialdehyde (MDA), on bovine brain synaptosomal ATPase activities and their membrane lipid organization were examined. When the synaptosomes were treated with HNE, this resulted in the decrease of Na^+-K^+-ATPase activity with the loss of sulfhydryl (SH) groups in the membrane proteins. In contrast, MDA treatment of the synaptosomes did not induce an appreciable decrease in the ATPase activity or a loss of SH groups. The decreases in ATPase activity and SH content by treatment with HNE were also observed, as a Na^+-K^+-ATPase preparation was used in place of the synaptosomes. On the other hand, HNE had very little effect on synaptosomal Ca^<2+>- and Mg^<2+>-ATPase activities. The results of the kinetic analysis of the Na^+-K^+-ATPase activity indicated that the decrease in the activity by HNE-modification is due to a decreased affinity for the substrate. ATP completely protected the ATPase from the HNE attack. Modification of the synaptosomes with HNE caused a decrease in the membrane lipid fluidity near the lipid/water interface, not the lipid layer interior. In addition, it was found that there is a good relationship between the lipid fluidity and the Na^+-K^+-ATPase activity under the presence of various concentrations of HNE, suggesting that the lipid dynamics are closely related to HNE-induced inhibition of the ATPase activity. On the other hand, MDA did not induce change in the membrane lipid fluidity. HNE and MDA are mainly incorporated into the lipid and protein fractions in the synaptosomal membranes, respectively. Based on these results, we proposed a possible mechanism of HNE-induced inhibition of synaptosomal Na^+-K^+-ATPase activity associated with alterations in the membrane lipid organization.
- 公益社団法人日本薬学会の論文
- 2003-06-01
著者
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OHYASHIKI Takao
Department of Biochemistry, Faculty of Pharmaceutical Science, Hokuriku University
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Ohyashiki Takao
Department Of Biochemistry Faculty Of Pharmaceutical Science Hokuriku University
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Miyake H
Department Of Clinical Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University
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MIYAKE Hiromi
Department of Clinical Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University
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KADOYA Akinori
Department of Clinical Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University
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Kadoya A
Department Of Clinical Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University
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Kadoya Akinori
Department Of Clinical Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University
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Ohyashiki Takao
Dep. Of Clinical Chemistry Fac. Of Pharmaceutical Sciences Hokuriku Univ.
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