Protective effect against 17beta-estradiol on neuronal apoptosis in hippocampus tissue following transient ischemia/recirculation in mongolian gerbils via down-regulation of tissue transglutaminase activity.
We analyzed the protective effect of 17beta-estradiol (17beta-ED) injection against delayed neuronal death in the hippocampus tissue of the brain in Mongolian gerbils after transient ischemia/recirculation treatment, especially in relation with bcl-2 gene expression and enzymatic activity changes of caspase-3 and tissue transglutaminase (tTGase). Daily intraperitoneal injection of 17beta-ED to the animal after the ischemia stimulated the expression of an apoptosis suppressor gene, bcl-2, in the hippocampal tissue for a week. The gradually increasing apoptotic enzyme activity of caspase-3 and increased number of TUNEL positive fragmented neuronal nuclei caused by ischemic attack in the gerbil brain were clearly suppressed by 17beta-ED administration. The reduced activity and enzyme protein of tTGase, a neurodegenerative marker of apoptosis in the hippocampus after ischemia, were also restored to nearly normal levels by 17beta-ED injection. These results suggest that daily 17beta-ED administration to the gerbil after transient ischemic insult with progressing neuronal deteriorative changes in hippocampus tissue can effectively prevent apoptotic changes through a molecular cascade involving gene expression regulation.
Fujita
K
K
Department of Physiology, School of Medicine, Fujita Health University, Toyoake, Aichi 470-1192, Japan. fujita-k@hoiku.ohkagakuen-u.ac.jp
Kato
T
T
Shibayama
K
K
Imada
H
H
Yamauchi
M
M
Yoshimoto
N
N
Miyachi
E
E
Nagata
Y
Y
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002545:Brain Ischemia; D053148:Caspase 3 / Q000378:metabolism; D015536:Down-Regulation; D004958:Estradiol / Q000008:administration & dosage / Q000378:metabolism*; D005849:Gerbillinae; D006624:Hippocampus / Q000166:cytology*; D020287:In Situ Nick-End Labeling; D008297:Male; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018696:Neuroprotective Agents / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015427:Reperfusion Injury; D011503:Transglutaminases / Q000378:metabolism*
D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D004958:Estradiol; D011503:Transglutaminases; D053148:Caspase 3