title: The neuroprotective role of TERT via an antiapoptotic mechanism in neonatal rats after hypoxia-ischemia brain injury.
abstract: Telomerase reverse transcriptase (TERT) can regulate cell apoptosis and proliferation. It has been shown that TERT expression can be induced in models of adult brain ischemia. In the present study, we investigated the role of TERT in ischemic neuronal death in neonatal hypoxic-ischemic rats model. Postnatal day 10 Sprague-Dawley rats were used to establish hypoxia-ischemia (HI) model and hypoxia alone (H) model. Pups were killed at 4, 8, 12, 24, or 48 h after the insult. Plasmid containing mock, TERT antisense or sense fragment mixed with Fugene HD was injected to the right lateral ventricle immediately after the insult respectively. Additional injection was performed after 24 h. Pups were sacrificed 24h after the administration. TERT and cleaved caspase-3 (CC3) expression were measured by Western blot. Apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. We found that H/HI treatment induced neuronal apoptosis and expression of TERT and CC3. However, TERT was higher in H than in HI pups whereas CC3 and apoptosis were opposite, TERT antisense plasmid markedly attenuated TERT expression induced by HI, upregualted CC3 expression, and increased apoptosis. Our results indicate that TERT might function as an anti-apoptotic protein by inhibiting activation of caspase-3, while further studies are needed to evaluate underlying mechanisms.
authors.affiliation: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Fengyan
authors.initials: F
authors.lastname: Zhao
authors.forename: Yi
authors.initials: Y
authors.lastname: Qu
authors.forename: Tao
authors.initials: T
authors.lastname: Xiong
authors.forename: Zhoujin
authors.initials: Z
authors.lastname: Duan
authors.forename: Qianghua
authors.initials: Q
authors.lastname: Ye
authors.forename: Dezhi
authors.initials: D
authors.lastname: Mu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D053148:Caspase 3 / Q000096:biosynthesis* / Q000378:metabolism; D004195:Disease Models, Animal; D020925:Hypoxia-Ischemia, Brain / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control*; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019098:Telomerase / Q000096:biosynthesis / Q000502:physiology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D019098:Telomerase; C505410:Casp3 protein, rat; D053148:Caspase 3