TY - JOUR
T1 - Estradiol reduces cytochrome c translocation and minimizes hippocampal damage caused by transient global ischemia in rat
AU - Bagetta, Giacinto
AU - Chiappetta, Olga
AU - Amantea, Diana
AU - Iannone, Michelangelo
AU - Rotiroti, Domenicantonio
AU - Costa, Alfredo
AU - Nappi, Giuseppe
AU - Corasaniti, Maria Tiziana
PY - 2004/9/16
Y1 - 2004/9/16
N2 - It is well-established that 17β-estradiol (17β-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 17β-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 6 h after reperfusion. 17β-E 2 (0.2 mg/kg, i.p.) given 1 h before ischemia minimized cytochrome c translocation and the latter effect was partially reversed by tamoxifen (0.25 mg/kg, i.p.). Bilateral cell counting revealed that delayed hippocampal damage typically caused by 4VO was abolished by 17β-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 17β-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.
AB - It is well-established that 17β-estradiol (17β-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 17β-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 6 h after reperfusion. 17β-E 2 (0.2 mg/kg, i.p.) given 1 h before ischemia minimized cytochrome c translocation and the latter effect was partially reversed by tamoxifen (0.25 mg/kg, i.p.). Bilateral cell counting revealed that delayed hippocampal damage typically caused by 4VO was abolished by 17β-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 17β-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.
KW - Cytochrome c translocation
KW - Mechanisms of neuroprotection by 17β-estradiol
KW - Transient global brain ischemia
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U2 - 10.1016/j.neulet.2004.06.062
DO - 10.1016/j.neulet.2004.06.062
M3 - Article
C2 - 15342140
AN - SCOPUS:4444260427
VL - 368
SP - 87
EP - 91
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 1
ER -