Increased hepatic telomerase activity in a rat model of iron overload: A role for altered thiol redox state?

Abstract

Telomeres are repeated sequences at chromosome ends that are incompletely replicated during mitosis. Telomere shortening caused by proliferation or oxidative damage culminates in replicative arrest and senescence, which may impair regeneration during chronic liver injury. While the effects of experimental liver injury on telomeres have received little attention, prior studies suggest that telomerase, the enzyme complex that catalyzes the addition of telomeric repeats, is protective in some rodent liver injury models. Thus, the aim of this study was to determine the effects of iron overload on telomere length and telomerase activity in rat liver. Mean telomere lengths were similar in ironloaded and control livers. However, telomerase activity was increased 3-fold by iron loading with no change in levels of TERT mRNA or protein. Because thiol redox state has been shown to modulate telomerase activity in vitro, hepatic thiols were assessed. Significant increases in GSH (1.5-fold), cysteine (15-fold), and glutamate cysteine ligase activity (1.5-fold) were observed in iron-loaded livers, while telomerase activity was inhibited by treatment with N-ethylmaleimide. This is the first demonstration of increased telomerase activity associated with thiol alterations in vivo. Enhanced telomerase activity may be an important factor contributing to the resistance of rodent liver to ironinduced damage.

In Vitro Sustained Differentiation of Rat Colon Epithelial Stem Cells

“…Activation of this receptor by extracellular Ca 2+ modulates the activities of MAPK and tyrosine kinases associated with cell proliferation [43,44]. However, Youshimura et al [45] with inhibition of telomerase activity [58,59]. Then cells entered terminal differentiation is usually coupled with permanent exit from the cell cycle.…”

The correlation between iron homeostasis and telomere maintenance

“…The increased telomerase activity may contribute to the resistance of rodent liver to iron-induced damage (Brown et al, 2007). Furthermore, the distributions of telomere length are similar between the control and iron overload groups, while the iron overload livers appear to have fewer telomeres in the shortest range (Brown et al, 2007).…”

“…However, in a rat iron overload model, telomerase activity increases three times relative to the control group, whereas the mean telomere length, TERT mRNA or protein level are same in both groups (Brown et al, 2007). The increased telomerase activity may contribute to the resistance of rodent liver to iron-induced damage (Brown et al, 2007).…”

“…A variety of studies have indicated that telomerase activity is markedly increased either in iron overload or iron deficient condition (Brown et al, 2007;Zhu et al, 2010;Mainous et al, 2013). In human, mutations in TERT have been implicated in predisposing patients to aplastic anemia, a disorder in which the bone marrow fails to produce blood cells (Calado and Young, 2012).…”

The Nuclear Compartmentation of Glutathione: Effect on Cell Cycle Progression

“…A number of reports have shown similar results. Brown et al, 2007 demonstrated for the first time in vivo that high hepatic glutathione levels correlate with increased telomerase activity. Also, the importance of glutathione regulation in telomerase activity has been proved in endothelial progenitor cells (EPC): impairment of antioxidant defences in EPC promoted oxidant mediated apoptosis and telomerase inactivation which subsequently lead to development and/or progression of atherothrombosis (Fujii et al, 2006).…”