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

Kyle E Brown; M Meleah Mathahs; Kimberly A Broadhurst; Mitchell C Coleman; Lisa A Ridnour; Warren N Schmidt; Douglas R Spitz

doi:10.1016/j.freeradbiomed.2006.10.039

Back

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

Journal article

Open access

Peer reviewed

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

Kyle E Brown, M Meleah Mathahs, Kimberly A Broadhurst, Mitchell C Coleman, Lisa A Ridnour, Warren N Schmidt and Douglas R Spitz

Free radical biology & medicine, Vol.42(2), pp.228-235

2007

DOI: 10.1016/j.freeradbiomed.2006.10.039

PMCID: PMC1820590

PMID: 17189828

Files and links (1)

url

https://www.ncbi.nlm.nih.gov/pmc/articles/1820590View

Open Access

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. Whereas 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 iron−loaded 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, whereas 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 iron-induced damage.

Oxidative Stress

Telomeres

Hemochromatosis

Free radicals

Glutamate cysteine ligase

Glutathione

Details

Title: Subtitle: Increased hepatic telomerase activity in a rat model of iron overload: A role for altered thiol redox state?
Creators: Kyle E Brown - Iowa City Veterans Administration Medical Center, Iowa City, IA, USA
M Meleah Mathahs - Iowa City Veterans Administration Medical Center, Iowa City, IA, USA
Kimberly A Broadhurst - Iowa City Veterans Administration Medical Center, Iowa City, IA, USA
Mitchell C Coleman - Program in Free Radical and Radiation Biology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA
Lisa A Ridnour - Radiation Biology Branch, National Cancer Institute, Bethesda, MD 20892, USA
Warren N Schmidt - Iowa City Veterans Administration Medical Center, Iowa City, IA, USA
Douglas R Spitz - Program in Free Radical and Radiation Biology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Free radical biology & medicine, Vol.42(2), pp.228-235
DOI: 10.1016/j.freeradbiomed.2006.10.039
PMID: 17189828
PMCID: PMC1820590
NLM abbreviation: Free Radic Biol Med
ISSN: 0891-5849
eISSN: 1873-4596
Publisher: Elsevier Inc
Language: English
Date published: 2007
Academic Unit: Gastroenterology and Hepatology; Pathology; Orthopedics and Rehabilitation; Radiation Oncology; Internal Medicine
Record Identifier: 9984040358102771

Metrics

11 Record Views

25 Times Cited - Web of Science