8-oxoguanine DNA glycosylase, but not Kin17 protein, is translocated and differentially regulated by estrogens in rat brain cells.
8-oxoguanine DNA glycosylase and Kin17 are proteins widely distributed and phylogenetically conserved in the CNS. 8-oxoguanine DNA glycosylase is a DNA repair enzyme that excises 7,8-dihydro-8-oxoguanine present in DNA damaged by oxidative stress. Kin17 protein is involved in DNA repair and illegitimate recombination in eukaryotic cells. The present study evaluates the effect of ovarian hormones on the expression of both proteins in the magnocellular paraventricular nucleus of the hypothalamus and the bed nucleus of the stria terminalis in female and male rat brains. In the paraventricular nucleus, ovariectomy induced a significant decrease in the number of 8-oxoguanine DNA glycosylase-positive nuclei as well as in their relative fluorescent intensity as compared with ovariectomized-estradiol treated and proestrous groups. Confocal microscopy observation demonstrated that oxoguanine DNA glycosylase protein is located in the Hoechst-dyed nuclei and cytoplasm in male and ovariectomized rats. Surprisingly, following estradiol administration to ovariectomized and proestrous rats, the 8-oxoguanine DNA glycosylase immunolabeling was observed in the nucleolus, the cytoplasm and the dendrites of cells, while Kin17 protein was always localized in the cell nuclei. In the bed nucleus of the stria terminalis, the number of 8-oxoguanine DNA glycosylase-positive nuclei during proestrous was significantly lower than the number obtained in males and ovariectomized rats and similar to the number of ovariectomized-estradiol-treated groups. In contrast to these observations, no significant differences were observed in the expression of kin17 protein. Our results suggest that estrogens differentially regulate the expression of 8-oxoguanine DNA glycosylase, but not that of Kin17 protein, in specific regions of the rat brain and that estradiol can translocate the 8-oxoguanine DNA glycosylase protein within nuclei and to other subcellular compartments.
Araneda
S
S
Physiologie Intégrative, Cellulaire et Moléculaire, UMR5123 CNRS/UCB Lyon 1. Bat Raphaël Dubois, Campus La Doua, 43 Bd du 11 Novembre 1918, 69622 Villeurbanne Cedex, France. araneda@univ-lyon1.fr
Pelloux
S
S
Radicella
J P
JP
Angulo
J
J
Kitahama
K
K
Gysling
K
K
Forray
M I
MI
D015100:3,3'-Diaminobenzidine; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002452:Cell Count; D002467:Cell Nucleus / Q000378:metabolism; D045647:DNA Glycosylases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000502:physiology*; D005260:Female; D005453:Fluorescence; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009532:Nickel; D009687:Nuclear Proteins / Q000378:metabolism*; D010052:Ovariectomy; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000378:metabolism; D011359:Proestrus / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism; D012686:Septal Nuclei / Q000166:cytology / Q000378:metabolism; D014018:Tissue Distribution / Q000187:drug effects
D004268:DNA-Binding Proteins; D004967:Estrogens; C489488:Kin protein, rat; D009687:Nuclear Proteins; D011960:Receptors, Estrogen; D015100:3,3'-Diaminobenzidine; C029938:nickel sulfate; D004958:Estradiol; D009532:Nickel; D045647:DNA Glycosylases; C483741:OGG1 protein, rat