The molecular events occur during MK-801-induced cytochrome oxidase subunit II down-regulation in GT1-7 cells

Tzu Ying Lee, Ke Li Tsai, Wen Sen Lee, Chin Hsu

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Previously, we showed that predominant expression of the N-methyl-D-aspartate (NMDA) receptor in the neurons of the sexually dimorphic nucleus of the preoptic area of male rats plays an important role in preventing neurons from apoptosis during sexual development. Blocking of the NMDA receptor by dizocilpine ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5, 10-iminemaleate (MK-801) causes down-regulation of some survival-related genes including cytochrome oxidase subunit II (COII), a mitochondria-encoded complex IV subunit, which in turn induces ATP depletion and the occurrence of apoptosis. The aim of this study is to investigate the molecular events during down-regulation of the COII gene expression induced by blocking of the NMDA receptor. Treatment of the GnRH cell line (GT1-7) with MK-801 caused 1) a decrease of intracellular calcium concentration ([Ca2+]i) after 20 h; 2) significant decreases of the levels of peroxisome proliferator-activated receptor γcoactivator-1 (PGC-1) mRNA and protein after 24 h; 3) down-regulation of COII mRNA after 36 h; and 4) the occurrence of neuronal apoptosis after 48 h. Accordingly, we hypothesize that blocking of the NMDA receptor may cause a decrease of the [Ca2+]i, which in turn inhibits the expressions of PGC-1 and COII and then leads to subsequent neuronal apoptosis.

Original languageEnglish
Pages (from-to)53-66
Number of pages14
JournalJournal of Molecular Endocrinology
Volume39
Issue number1-2
DOIs
Publication statusPublished - Jul 2007

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Dizocilpine Maleate
Electron Transport Complex IV
N-Methyl-D-Aspartate Receptors
Down-Regulation
Apoptosis
Neurons
Messenger RNA
Sexual Development
Peroxisome Proliferator-Activated Receptors
Preoptic Area
Gonadotropin-Releasing Hormone
Mitochondria
Adenosine Triphosphate
Calcium
Gene Expression
Cell Line
Genes
Proteins

ASJC Scopus subject areas

  • Endocrinology

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The molecular events occur during MK-801-induced cytochrome oxidase subunit II down-regulation in GT1-7 cells. / Lee, Tzu Ying; Tsai, Ke Li; Lee, Wen Sen; Hsu, Chin.

In: Journal of Molecular Endocrinology, Vol. 39, No. 1-2, 07.2007, p. 53-66.

Research output: Contribution to journalArticle

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