Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/17736
Title: Human telomerase reverse transcriptase (hTERT) overexpression modulates intracellular redox balance and protects cancer cells from apoptotic cell death
Authors: INTHRANI D/O RAJA INDRAN
Keywords: hTERT, mitochondria, ROS, apoptosis, antioxidant
Issue Date: 27-Oct-2009
Source: INTHRANI D/O RAJA INDRAN (2009-10-27). Human telomerase reverse transcriptase (hTERT) overexpression modulates intracellular redox balance and protects cancer cells from apoptotic cell death. ScholarBank@NUS Repository.
Abstract: The human telomerase reverse transcriptase (hTERT) is the catalytic subunit of the telomerase holoenzyme. Evidence is accumulating to link hTERT to activities other than telomere maintenance and immortalization. Here we show that hTERT overexpression not only reduces the basal cellular ROS levels but also inhibits endogenous ROS production in response to stimuli that induce intracellular ROS generation. Conversely, siRNA-mediated gene silencing of hTERT potentiated the increase in cellular ROS levels following exposure to oxidative stress. This anti-oxidant effect of hTERT is mediated via a significant increase in the ratio of reduced to oxidized glutathione (GSH:GSSG) as well as efficient recovery of the oxidized peroxiredoxin to its non-oxidized form. Our data also provide evidence for mitochondrial localization of hTERT, and a significantly higher activity of cytochrome c oxidase, the rate-limiting enzyme in the mitochondrial electron transport chain, in hTERT overexpressing cells. To ascertain whether the improved mitochondrial function and antioxidant effect of hTERT could provide cancer cells with a survival advantage, the effect of oxidative stress on mitochondrial apoptosis was evaluated. Indeed, hTERT overexpressing cells inhibited cytosolic acidification, translocation of Bax, the drop in mitochondrial transmembrane potential, the release of cytochrome C to the cytosol, and cell death. Taken together, these data demonstrate a hitherto undefined role of hTERT in alleviating cellular ROS levels by way of potentiating the cellular anti-oxidant defense systems, and in doing so endowing cancer cells with the ability to evade death stimuli.
URI: http://scholarbank.nus.edu.sg/handle/10635/17736
Appears in Collections:Ph.D Theses (Open)

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