Expression of telomerase in normal and malignant rat hepatic epithelia

Golubovskaya, Vita M.; Presnell, Sharon C.; Hooth, Michelle J.; Smith, Gary J.

doi:10.1038/sj.onc.1201278

Cited by 19 publications

(22 citation statements)

References 26 publications

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“…Most differentiated human somatic cells lack both telomerase activity and TERT expression, while germ cells, some stem cells and a majority of cancers demonstrate both telomerase activity and TERT expression. In contrast, many tissues of adult rodents, including the liver, show persistent telomerase activity and TERT expression [23][24][25][26]. Consistent with these data, we observed a low level of telomerase activity and TERT expression in control rat livers.…”

Section: Discussionsupporting

confidence: 89%

“…Relatively little attention has been paid to the effects of disease models on telomeres in rodents, perhaps because of the known differences in telomere length and telomerase activity among human and rodent species [18,[23][24][25][26]. Notwithstanding the species differences, data implying a pathogenic role of telomere shortening in several forms of human pathology suggest that assessment of the effects of disease models on rodent telomeres may provide important insights into the relationship between telomeres and disease processes.…”

Section: Discussionmentioning

confidence: 99%

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

Brown

Mathahs²,

Broadhurst³

et al. 2007

Free Radical Biology and Medicine

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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.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

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

Brown

Mathahs²,

Broadhurst³

et al. 2007

Free Radical Biology and Medicine

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“…Cell extracts for assay of telomerase were prepared as described (Golubovskaya et al, 1997). The concentration of protein was measured for each extract with bicinchroninic acid protein assay kit (Pierce Chemical Co).…”

Section: Telomerase Assaymentioning

confidence: 99%

“…Telomerase activity was detected by the PCR-mediated, telomeric-repeat ampli®cation protocol (TRAP) described by Kim et al, 1994). The initial telomerase extension reaction and the secondary PCR reaction were performed in dierent tubes Nakayama et al, 1997), as described (Golubovskaya et al, 1997).…”

Section: Telomerase Assaymentioning

confidence: 99%

Chromosomal instability is correlated with telomere erosion and inactivation of G2 checkpoint function in human fibroblasts expressing human papillomavirus type 16 E6 oncoprotein

et al. 1998

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Cell cycle checkpoints and tumor suppressor gene functions appear to be required for the maintenance of a stable genome in proliferating cells. In this study chromosomal destabilization was monitored in relation to telomere structure, lifespan control and G2 checkpoint function. Replicative senescence was inactivated in secondary cultures of human skin ®broblasts by expressing the human papillomavirus type 16 (HPV-16) E6 oncoprotein to inactivate p53. Chromosome aberrations were enumerated during in vitro aging of isogenic control (F5neo) and HPV-16E6-expressing (F5E6) ®broblasts. We found that structural and numerical aberrations in chromosomes were signi®cantly increased in F5E6 cells during aging in vitro and¯uorescence in situ hybridization (FISH) analysis using chromosome-speci®c probes demonstrated the occurrence of rearrangements involving chromosome 4 and 6 in genetically unstable F5E6 cells. Flow cytometry and karyotypic analyses revealed increased polyploidy and aneuploidy in F5E6 cells only at passages 416, although these cells displayed defective mitotic spindle checkpoint function associated with inactivation of p53 at passages 5 and 16. G2 checkpoint function was con®rmed to be gradually but progressively inactivated during in vitro aging of E6-expressing cells. Aging of F5neo ®broblasts was documented during in vitro passaging by induction of a senescence-associated marker, pH 6.0 lysosomal b-galactosidase. F5E6 cells displayed extension of in vitro lifespan and did not induce b-galactosidase at high passage. Erosion of telomeres during in vitro aging of telomerase-negative F5neo cells was demonstrated by Southern hybridization and by quantitative FISH analysis on an individual cell level. Telomeric signals diminished continuously as F5neo cells aged in vitro being reduced by 80% near the time of replicative senescence. Telomeric signals detected by FISH also decreased continuously during aging of telomerasenegative F5E6 cells, but telomeres appeared to be stabilized at passage 34 when telomerase was expressed. Chromosomal instability in E6-expressing cells was correlated (P50.05) with both loss of telomeric signals and inactivation of G2 checkpoint function. The results suggest that chromosomal stability depends upon a complex interaction among the systems of telomere length maintenance and cell cycle checkpoints.

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“…Increase in telomerase activity may contribute to this almost endless capacity of hepatocytes to divide in vivo. Moderate (up to twofold) increase in telomerase activity was found in regenerating rat hepatocytes, but there is a detectable telomerase activity in quiescent rodent livers which is not the case in humans (17). A study in pig model, which better fits human telomerase biology with no activity in quiescent livers, revealed even fivefold increase in telomerase activity after two thirds partial hepatectomy (63).…”

Section: Importance and Description Of The Liver Regenerative Capacitymentioning

confidence: 99%

Studying Liver Regeneration by Means of Molecular Biology: How Far We Are in Interpreting the Findings?

Rychtrmoc

Libra

Bunček

et al. 2009

Acta Med. (Hradec Kralove, Czech Repub.)

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Summary: Liver regeneration in mammals is a unique phenomenon attracting scientific interest for decades. It is a valuable model for basic biology research of cell cycle control as well as for clinically oriented studies of wide and heterogeneous group of liver diseases. This article provides a concise review of current knowledge about the liver regeneration, focusing mainly on rat partial hepatectomy model. The three main recognized phases of the regenerative response are described. The article also summarizes history of molecular biology approaches to the topic and finally comments on obstacles in interpreting the data obtained from large scale microarray-based gene expression analyses.

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Expression of telomerase in normal and malignant rat hepatic epithelia

Cited by 19 publications

References 26 publications

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

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

Chromosomal instability is correlated with telomere erosion and inactivation of G2 checkpoint function in human fibroblasts expressing human papillomavirus type 16 E6 oncoprotein

Studying Liver Regeneration by Means of Molecular Biology: How Far We Are in Interpreting the Findings?

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