Effects of aripiprazole and clozapine on the treatment of glycolytic carbon in PC12 cells

Akira Ota, Akira Nakashima, Yoko S. Kaneko, Keiji Mori, Hiroshi Nagasaki, Takeshi Takayanagi, Mitsuyasu Itoh, Kazunao Kondo, Toshiharu Nagatsu, Miyuki Ota

研究成果: Article

5 引用 (Scopus)

抄録

Aripiprazole is the only atypical antipsychotic drug known to cause the phosphorylation of AMP-activated protein kinase (AMPK) in PC12 cells. However, the molecular mechanisms underlying this phosphorylation in aripiprazole-treated PC12 cells have not yet been clarified. Here, using PC12 cells, we show that these cells incubated for 24 h with aripiprazole at 50 μM and 25 mM glucose underwent a decrease in their NAD+/NADH ratio. Aripiprazole suppressed cytochrome c oxidase (COX) activity but enhanced the activities of pyruvate dehydrogenase (PDH), citrate synthase and Complex I. The changes in enzyme activities coincided well with those in NADH, NAD+, and NAD+/NADH ratio. However, the bioenergetic peril judged by the lowered COX activity might not be accompanied by excessive occurrence of apoptotic cell death in aripiprazole-treated cells, because the mitochondrial membrane potential was not decreased, but rather increased. On the other hand, when PC12 cells were incubated for 24 h with clozapine at 50 lM and 25 mM glucose, the NAD+/NADH ratio did not change. Also, the COX activity was decreased; and the PDH activity was enhanced. These results suggest that aripiprazole-treated PC12 cells responded to the bioenergetic peril more effectively than the clozapine-treated ones to return the ATP biosynthesis back toward its ordinary level. This finding might be related to the fact that aripiprazole alone causes phosphorylation of AMPK in PC12 cells.

元の言語English
ページ(範囲)1327-1342
ページ数16
ジャーナルJournal of Neural Transmission
119
発行部数11
DOI
出版物ステータスPublished - 01-11-2012

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Clozapine
PC12 Cells
NAD
Carbon
Oxidoreductases
AMP-Activated Protein Kinases
Phosphorylation
Pyruvic Acid
Energy Metabolism
Glucose
Citrate (si)-Synthase
Glycogen Synthase
Aripiprazole
Mitochondrial Membrane Potential
Electron Transport Complex IV
Antipsychotic Agents
Cell Death
Adenosine Triphosphate
Enzymes

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry

これを引用

Ota, Akira ; Nakashima, Akira ; Kaneko, Yoko S. ; Mori, Keiji ; Nagasaki, Hiroshi ; Takayanagi, Takeshi ; Itoh, Mitsuyasu ; Kondo, Kazunao ; Nagatsu, Toshiharu ; Ota, Miyuki. / Effects of aripiprazole and clozapine on the treatment of glycolytic carbon in PC12 cells. :: Journal of Neural Transmission. 2012 ; 巻 119, 番号 11. pp. 1327-1342.
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abstract = "Aripiprazole is the only atypical antipsychotic drug known to cause the phosphorylation of AMP-activated protein kinase (AMPK) in PC12 cells. However, the molecular mechanisms underlying this phosphorylation in aripiprazole-treated PC12 cells have not yet been clarified. Here, using PC12 cells, we show that these cells incubated for 24 h with aripiprazole at 50 μM and 25 mM glucose underwent a decrease in their NAD+/NADH ratio. Aripiprazole suppressed cytochrome c oxidase (COX) activity but enhanced the activities of pyruvate dehydrogenase (PDH), citrate synthase and Complex I. The changes in enzyme activities coincided well with those in NADH, NAD+, and NAD+/NADH ratio. However, the bioenergetic peril judged by the lowered COX activity might not be accompanied by excessive occurrence of apoptotic cell death in aripiprazole-treated cells, because the mitochondrial membrane potential was not decreased, but rather increased. On the other hand, when PC12 cells were incubated for 24 h with clozapine at 50 lM and 25 mM glucose, the NAD+/NADH ratio did not change. Also, the COX activity was decreased; and the PDH activity was enhanced. These results suggest that aripiprazole-treated PC12 cells responded to the bioenergetic peril more effectively than the clozapine-treated ones to return the ATP biosynthesis back toward its ordinary level. This finding might be related to the fact that aripiprazole alone causes phosphorylation of AMPK in PC12 cells.",
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Ota, A, Nakashima, A, Kaneko, YS, Mori, K, Nagasaki, H, Takayanagi, T, Itoh, M, Kondo, K, Nagatsu, T & Ota, M 2012, 'Effects of aripiprazole and clozapine on the treatment of glycolytic carbon in PC12 cells', Journal of Neural Transmission, 巻. 119, 番号 11, pp. 1327-1342. https://doi.org/10.1007/s00702-012-0782-2

Effects of aripiprazole and clozapine on the treatment of glycolytic carbon in PC12 cells. / Ota, Akira; Nakashima, Akira; Kaneko, Yoko S.; Mori, Keiji; Nagasaki, Hiroshi; Takayanagi, Takeshi; Itoh, Mitsuyasu; Kondo, Kazunao; Nagatsu, Toshiharu; Ota, Miyuki.

:: Journal of Neural Transmission, 巻 119, 番号 11, 01.11.2012, p. 1327-1342.

研究成果: Article

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T1 - Effects of aripiprazole and clozapine on the treatment of glycolytic carbon in PC12 cells

AU - Ota, Akira

AU - Nakashima, Akira

AU - Kaneko, Yoko S.

AU - Mori, Keiji

AU - Nagasaki, Hiroshi

AU - Takayanagi, Takeshi

AU - Itoh, Mitsuyasu

AU - Kondo, Kazunao

AU - Nagatsu, Toshiharu

AU - Ota, Miyuki

PY - 2012/11/1

Y1 - 2012/11/1

N2 - Aripiprazole is the only atypical antipsychotic drug known to cause the phosphorylation of AMP-activated protein kinase (AMPK) in PC12 cells. However, the molecular mechanisms underlying this phosphorylation in aripiprazole-treated PC12 cells have not yet been clarified. Here, using PC12 cells, we show that these cells incubated for 24 h with aripiprazole at 50 μM and 25 mM glucose underwent a decrease in their NAD+/NADH ratio. Aripiprazole suppressed cytochrome c oxidase (COX) activity but enhanced the activities of pyruvate dehydrogenase (PDH), citrate synthase and Complex I. The changes in enzyme activities coincided well with those in NADH, NAD+, and NAD+/NADH ratio. However, the bioenergetic peril judged by the lowered COX activity might not be accompanied by excessive occurrence of apoptotic cell death in aripiprazole-treated cells, because the mitochondrial membrane potential was not decreased, but rather increased. On the other hand, when PC12 cells were incubated for 24 h with clozapine at 50 lM and 25 mM glucose, the NAD+/NADH ratio did not change. Also, the COX activity was decreased; and the PDH activity was enhanced. These results suggest that aripiprazole-treated PC12 cells responded to the bioenergetic peril more effectively than the clozapine-treated ones to return the ATP biosynthesis back toward its ordinary level. This finding might be related to the fact that aripiprazole alone causes phosphorylation of AMPK in PC12 cells.

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