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

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)50-55
Number of pages6
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume117
Issue number1-3
DOIs
Publication statusPublished - 2009 Oct
Externally publishedYes

Keywords

  • ATP production
  • Corticosterone
  • Glucocorticoid
  • Mitochondria
  • Stress

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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