Direct effects of corticosterone on ATP production by mitochondria from immortalized hypothalamic GT1-7 neurons

Chisako Fujita, Fumito Ichikawa, Toshiaki Teratani, Gen Murakami, Takahiro Okada, Masaki Shinohara, Suguru Kawato, Yoshihiro Ohta

研究成果: Article査読

10 被引用数 (Scopus)

抄録

Glucocorticoids are known to decrease intracellular ATP levels in the brain. This study was performed to investigate whether corticosterone at physiological levels depresses mitochondrial ATP production by directly acting on mitochondria. Mitochondria were isolated from immortalized hypothalamic GT1-7 neurons. ATP levels were determined using a luciferase-luciferin assay. When malate, α-ketoglutarate or pyruvate was used as a respiration substrate, corticosterone at ≥100 nM decreased ATP production by 10%. In contrast, corticosterone did not affect ATP production when succinate or N,N,N′,N′-tetramethyl-p-phenylenediamine + ascorbate were used. To investigate the specificity of corticosterone inhibition, we examined several steroids. All steroids tested suppressed mitochondrial ATP production by 10% at a concentration of 100 nM, in a manner similar to that of corticosterone. To examine the effects of corticosterone on GT1-7 cell physiology, we incubated GT1-7 cells with t-butyl hydroperoxide (t-BuOOH) with corticosterone. Corticosterone largely enhanced t-BuOOH-induced cell death. These results indicate that corticosterone non-specifically inhibits mitochondrial ATP production by suppressing electron transfer from NADH to the electron transfer chain through complex I. Partial inhibition of mitochondrial ATP production by corticosterone may contribute to oxidative stress-induced cell death.

本文言語English
ページ(範囲)50-55
ページ数6
ジャーナルJournal of Steroid Biochemistry and Molecular Biology
117
1-3
DOI
出版ステータスPublished - 2009 10
外部発表はい

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 生化学
  • 分子医療
  • 分子生物学
  • 内分泌学
  • 臨床生化学
  • 細胞生物学

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