Telomerase is a ribonucleoprotein DNA polymerase that has been associated with cell proliferation, cell survival and apoptosis inhibition. Telomerase is regulated by specific growth factors, cytokines and hormones. The present study examines the effect of GH on telomerase activity and identifies the signal transduction pathway involved in this process in Chinese hamster ovary (CHO)4 cells, which express rat GH receptor cDNA. Telomeric repeat amplification protocol assays demonstrated that treating CHO4 cells with increasingly high doses of GH up-regulated telomerase activity with the maximum activation at 24 h. Similarly, GH activated telomerase in another cell system, primary cultures of rat hepatocytes. The telomerase activation in CHO4 cells was produced with an increase in hamster telomerase catalytic subunit (hamTERT) mRNA expression. The telomerase activity induced by GH was specifically blocked by the phosphatidylinositol 3 -kinase (PI3-K) inhibitor, LY294002, but not by the MAP kinase kinase inhibitor, PD98059. These findings suggest that GH could activate telomerase through the direct activation of TERT transcription, as well as through the PI3-K signalling pathway.
The present work determined the minimum alveolar concentrations (MAC) of halothane, isoflurane and sevoflurane in adult female gerbils (n ¼ 24). Animals were placed in a chamber for anaesthetic induction before performing tracheal intubation. The tracheal tube was connected to a non-rebreathing circuit with minimal dead space. Body temperature, blood pressure, heart and respiratory rates and end-tidal volatile anaesthetic levels were measured continuously. MAC was determined using a standard noxious stimulus (tail-clamp). All experiments were performed at the same time of the day, body temperature was maintained constant and blood-gas analysis was performed to confirm that values were within normal limits. The mean + SD MAC values were 1.06 + 0.11% halothane (n ¼ 8), 1.55 + 0.08% isoflurane (n ¼ 8) and 2.90 + 0.12% sevoflurane (n ¼ 7). Cardiovascular parameters at 1Â MAC did not differ significantly among anaesthetics but the respiratory rate was significantly higher in the halothane group than in the isoflurane and sevoflurane groups. The SpO 2 values recorded throughout anaesthesia and the pH and partial oxygen pressure values determined at the end of the study did not differ among the studied anaesthetics at 1Â MAC. These data suggest that the MAC for halogenated inhalant anaesthetics in gerbils is lower than the average MAC values obtained in rats and mice.
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