Estradiol reduces cytochrome c translocation and minimizes hippocampal damage caused by transient global ischemia in rat.
It is well-established that 17beta-estradiol (17beta-E(2)) confers neuroprotection to male and female rats exposed to focal cerebral ischemia, while less is known about the effects of the hormone under conditions of transient global ischemia. Since translocation of cytochrome c from the mitochondria to the cytosol is a critical step in apoptotic cell death after cerebral ischemia, we have investigated whether 17beta-E(2) interferes with such mechanism to exert neuroprotection. Global ischemia, induced in male Wistar rats by 5-min 4 vessel occlusion (4VO), resulted in a significant increase of cytosolic cytochrome c (cyt-c) levels as detected by Western blotting at 6h after reperfusion. 17beta-E(2) (0.2mg/kg, i.p.) given 1h before ischemia minimized cytochrome c translocation and the latter effect was partially reversed by tamoxifen (0.25mg/kg, i.p.). Bilateral cell counting revealed that delayed hippocampal damage typically caused by 4VO was abolished by 17beta-E(2) and this was partially reversed by tamoxifen in the CA3 subregion, but not in CA1/CA2 or CA4. These findings provide the original observation that 17beta-E(2) reduces delayed hippocampal damage caused by 4VO in male rats and blocks cytochrome c translocation during the early stages of neuronal death, thus providing an important mechanism involved in estrogen-mediated neuroprotection.
Bagetta
Giacinto
G
Department of Pharmacobiology, University of Calabria,Via Pietro Bucci, 87036 Arcavacata di Rende (CS), Italy. gbagett@tin.it
Chiappetta
Olga
O
Amantea
Diana
D
Iannone
Michelangelo
M
Rotiroti
Domenicantonio
D
Costa
Alfredo
A
Nappi
Giuseppe
G
Corasaniti
Maria Tiziana
MT
D000818:Animals; D015153:Blotting, Western; D045304:Cytochromes c / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000473:pathology*; D002546:Ischemic Attack, Transient / Q000473:pathology*; D008297:Male; D018696:Neuroprotective Agents; D051381:Rats; D017208:Rats, Wistar; D013629:Tamoxifen / Q000494:pharmacology; D014178:Translocation, Genetic / Q000235:genetics
D004965:Estrogen Antagonists; D018696:Neuroprotective Agents; D013629:Tamoxifen; D004958:Estradiol; D045304:Cytochromes c