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Oestrogen Influences on Mitochondrial Gene Expression and Respiratory Chain Activity in Cortical and Mesencephalic Astrocytes
Author(s) -
Araújo G. W.,
Beyer C.,
Arnold S.
Publication year - 2008
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/j.1365-2826.2008.01747.x
Subject(s) - respiratory chain , mitochondrial respiratory chain , mitochondrion , biology , respiratory system , oxidative phosphorylation , endocrinology , medicine , mitochondrial dna , central nervous system , microbiology and biotechnology , biochemistry , gene , anatomy
The regulation of mitochondrial energy metabolism plays an essential role in the central nervous system (CNS). Abnormalities of the mitochondrial respiratory chain often accompany neurodegenerative diseases. This makes mitochondria a perfect target for strategies of cellular protection against toxic compounds and pathological conditions. Steroid hormones, such as oestrogen, are well‐known to fulfil a protective role in the brain during ischaemic and degenerative processes. Because astrocytes function as the major energy supplier in the CNS, we have analysed oestrogen effects on the mitochondrial respiratory chain of this cell type. In our studies, we applied semi‐ and quantitative polymerase chain reaction analysis of gene expression and polarographic measurements of the respiratory chain activity of mitochondria. We observed that structural and functional properties were regulated dependent on the oestrogen exposure time and the brain region, but independent of the nuclear oestrogen receptors. We could demonstrate that long‐term oestrogen exposure increases the subunit gene expression of respiratory chain complexes and the mitochondrial DNA content, thereby indicating an up‐regulation of the amount of mitochondria per cell together with an increase of mitochondrial energy production. This could represent an important indirect mechanism by which long‐term oestrogen exposure protects neurones from cell death under neurotoxic conditions. On the other hand, we observed short‐term effects of oestrogen on the activity of mitochondrial, proton‐pumping respiratory chain complexes. In astrocytes from the cortex, respiratory chain activity was decreased, whereas it was increased in astrocytes from the mesencephalon. An increased production of reactive oxygen species would be the consequence of an increased respiratory chain activity in mesencephalic astrocytes. This could explain the different efficiencies of oestrogen‐mediated short‐term protection in distinct brain regions, but also indicates the limitations for a therapeutic short‐term application of oestrogen.