Glutamate regulates the activity of topoisomerase I in mouse cerebellum.

Abstract:

:Topoisomerase I (topo I) is a nuclear enzyme which participates in most DNA transactions. It was shown to be inhibited in depolarized neurons by poly adenosine diphosphate (ADP)-ribosylation of the enzyme protein. We demonstrated previously an age and sex dependent topo I activity and enzyme protein level in the various regions of mouse brain. A specific distribution pattern of topo I was observed and the inhibitory neurons exhibited the highest enzyme activity and protein level in both the nucleus and the cytoplasm. Here, we show that neurotransmitters (glutamate and gamma-aminobutyric acid (GABA)) regulate the activity of topo I in mouse cerebellum sections. Glutamate exhibited a significant time-dependent inhibition of topo I activity but no effect of the enzyme protein level. GABA in contrary only slightly and transiently inhibited topo I activity. The inhibitory effect of glutamate was mediated by Ca(+2) and by ADP-ribosylation of topo I protein and the glutamate ionotropic receptors were involved. Glutamate also diminished the inhibitory effect of topotecan on topo I. These results point to distinct and highly specific effects of the major neurotransmitters on topo I activity in the cerebellum suggesting that topo I possesses a specific role in the brain which differs from its known biological functions.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

Zehorai E,Eitan E,Hershfinkel M,Sekler I,Priel E

doi

10.1007/s12035-008-8044-x

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

242-52

issue

3

eissn

0893-7648

issn

1559-1182

journal_volume

38

pub_type

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