1alpha,25-dihydroxy-vitamin D3 in combination with 17beta-estradiol lowers the cortical expression of heat shock protein-27 following experimentally induced focal cortical ischemia in rats.
1alpha,25-(OH)(2)-vitamin-D(3) (1,25-D(3)) and 17beta-estradiol are both known to act neuroprotective in certain experimental in vitro and in vivo settings. We studied the effects of 1,25-D(3) or 17beta-estradiol or their combined application on heat shock protein-27 (HSP-27) distribution after focal cortical ischemia using the photothrombosis model. HSP-27 is a well-established marker of the cerebral oxidative stress response and a potent inhibitor of apoptosis. Lesioned rats were injected i.p. one hour after injury with either 1 microg 1,25-D(3)/kg or 7 microg 17beta-estradiol/kg or a combination of both steroids. Groups of non-lesioned steroid-treated rats and lesioned, solvent-treated rats served as controls. Treatment with both steroids did not affect the size of the lesion. In addition, 17beta-estradiol resulted in significant reduction of HSP-27 induction, whereas the combination of 1,25-D(3)+17beta-estradiol resulted in a highly significant reduction of HSP-27 within the infracted cerebral cortex, indicating that both steroids act synergistically in a protective manner.
Losem-Heinrichs
Eva
E
C. & O. Vogt Institute for Brain Research, University St. 1, 40225 Düsseldorf, Germany.
Görg
Boris
B
Redecker
Christoph
C
Schleicher
Axel
A
Witte
Otto W
OW
Zilles
Karl
K
Bidmon
Hans-J
HJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D004357:Drug Synergism; D004958:Estradiol / Q000008:administration & dosage*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014807:Vitamin D / Q000008:administration & dosage* / Q000031:analogs & derivatives*
D015415:Biomarkers; D006360:Heat-Shock Proteins; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D004958:Estradiol