title: HIF-1-α and survivin involved in the anti-apoptotic effect of 2ME2 after global ischemia in rats.
abstract: Survivin is an anti-apoptotic gene that decreases the apoptosis by depressing the expression of caspase-3. Hypoxia-inducible factor-1-alpha (HIF-1-alpha) is a transcription factor specifically activated by hypoxia. 2-methoxyestradiol (2ME2) is an estradiol derivative and a known HIF-1-alpha inhibitor. 2ME2 decreased apoptosis by inhibiting HIF-1-alpha. The aim of the present study was to investigate if survivin is involved in the anti-apoptotic effect of 2ME2. Male adult rats were used to make the global ischemia (GI) model. Ten minutes after GI, 2ME2 was injected intraperitoneally (16 mg/kg weight). Rats were killed at 6 hours, 12 hours, 24 hours, 48 hours, 96 hours, and 7 days. GI produced a marked increase in HIF-1-alpha expressions in the hippocampus at 6 hours and peaked at 48-96 hours. The expressions of survivin and caspase-3 were increased lightly in a similar time course. These molecular changes were accompanied by massive cell loss and apoptosis in the hippocampal regions. 2ME2 treatment reduced the expression of HIF-1-alpha, increased survivin expression, and decreased the expression of caspase-3. These results indicate that survivin and HIF-1-alpha were involved in the anti-apoptotic effect of 2ME2 treated following GI. 2ME2 may decrease the HIF-1-alpha expression, up-regulate the survivin expression, inhibit the expression of caspase-3, and finally reduce apoptosis after GI.
authors.affiliation: Department of Physiology, Shandong University School of Medicine, Jinan, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Zuo-Li
authors.initials: ZL
authors.lastname: Xia
authors.forename: Lian-Bi
authors.initials: LB
authors.lastname: Chen
mesh_terms: D000077584:2-Methoxyestradiol; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077022:Survivin; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D051017:Apoptosis Regulatory Proteins; C516989:Birc5 protein, rat; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008869:Microtubule-Associated Proteins; D000077022:Survivin; D004958:Estradiol; D000077584:2-Methoxyestradiol