GERD is associated with shortened telomeres in the squamous epithelium of the distal esophagus

2007 ◽  
Vol 293 (1) ◽  
pp. G19-G24 ◽  
Author(s):  
Rhonda F. Souza ◽  
Tisha Lunsford ◽  
Ruben D. Ramirez ◽  
Xi Zhang ◽  
Edward L. Lee ◽  
...  
Keyword(s):  
Telomere Length ◽  
Barrett’S Esophagus ◽  
Dna Sequences ◽  
Barrett's Esophagus ◽  
Oxidative Dna Damage ◽  
Squamous Epithelium ◽  
Telomerase Activity ◽  
Mucosal Healing ◽  
Distal Esophagus ◽  
Amplification Protocol

Telomeres are repetitive DNA sequences located at the ends of chromosomes. Telomeres are shortened by repeated cell divisions and by oxidative DNA damage, and cells with critically shortened telomeres cannot divide. We hypothesized that chronic gastroesophageal reflux disease (GERD)-induced injury of the esophageal squamous epithelium results in progressive telomeric shortening that eventually might interfere with mucosal healing. To address our hypothesis, we compared telomere length and telomerase activity in biopsy specimens of esophageal squamous epithelium from GERD patients and control patients. Endoscopic biopsies were taken from the esophageal squamous epithelium of 38 patients with GERD [10 long-segment Barrett's esophagus (LSBE), 15 short-segment (SSBE), 13 GERD without Barrett's esophagus] and 16 control patients without GERD. Telomere length was assessed using the terminal restriction fragment assay, and telomerase activity was studied by the PCR-based telomeric repeat amplification protocol assay. Patients with GERD had significantly shorter telomeres in the distal esophagus than controls [8.3 ± 0.5 vs. 10.9 ± 1.5 (SE) Kbp, P = 0.043]. Among the patients with GERD, telomere length in the distal esophagus did not differ significantly in those with and without Barrett's esophagus (LSBE 7.9 ± 0.8, SSBE 8.6 ± 0.9, GERD without BE 8.7 ± 1.0 Kbp). No significant differences in telomerase activity in the distal esophagus were noted between patients with GERD and controls (4.0 ± 0.39 vs. 5.2 ± 0.53 RIUs). Telomeres in the squamous epithelium of the distal esophagus of patients who have GERD, with and without Barrett's esophagus, are significantly shorter than those of patients without GERD despite similar levels of telomerase activity.

scholarly journals Telomere Length in Valve Tissue Is Shorter in Individuals With Aortic Stenosis and in Calcified Valve Areas

2021 ◽  
Vol 9 ◽  
Author(s):  
Ilona Saraieva ◽  
Athanase Benetos ◽  
Carlos Labat ◽  
Anders Franco-Cereceda ◽  
Magnus Bäck ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Stenosis ◽  
Telomere Length ◽  
Telomerase Activity ◽  
Aortic Valves ◽  
Fragment Analysis ◽  
Replacement Surgery ◽  
Age Related ◽  
Amplification Protocol ◽  
Telomere Restriction Fragment

BackgroundShort telomere length (TL) is associated with age-related diseases, in particular cardiovascular diseases. However, whether the onset and course of aortic stenosis (AS) is linked to TL in aortic valves remains unknown.ObjectivesTo assess telomere dynamics (TL and telomerase activity) in aortic valves and the possible implication of TL in onset and course of AS.MethodsDNA was extracted from aortic valves obtained from 55 patients (78.2% men; age, 37–79 years), who had undergone replacement surgery due to AS (AS group, n = 32), aortic valve regurgitation and aortic dilation (Non-AS group, n = 23). TL was measured by telomere restriction fragment analysis (TRF) in calcified and non-calcified aortic valve areas. Telomerase activity was evaluated using telomerase repeat amplification protocol (TRAP) in protein extracts from non-calcified and calcified areas of valves obtained from 4 additional patients (50% men; age, 27–70 years).ResultsTL was shorter in calcified aortic valve areas in comparison to non-calcified areas (n = 31, 8.58 ± 0.73 kb vs. 8.12 ± 0.75 kb, p < 0.0001), whereas telomerase activity was not detected in any of those areas. Moreover, patients from AS group displayed shorter telomeres in non-calcified areas than those from the Non-AS group (8.40 ± 0.64 kb vs. 8.85 ± 0.65, p = 0.01).ConclusionsShort telomeres in aortic valves may participate in the development of AS, while concurrently the calcification process seems to promote further local decrease of TL in calcified areas of valves.

scholarly journals MicroRNA Expression Differentiates Squamous Epithelium from Barrett’s Esophagus and Esophageal Cancer

2013 ◽  
Vol 58 (11) ◽  
pp. 3178-3188 ◽  
Author(s):  
Katherine S. Garman ◽  
Kouros Owzar ◽  
Elizabeth R. Hauser ◽  
Kristen Westfall ◽  
Blair R. Anderson ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Squamous Epithelium ◽  
Microrna Expression

33 TELOMERASE ACTIVITIES IN CLONED BEAGLE DOGS

2015 ◽  
Vol 27 (1) ◽  
pp. 109
Author(s):  
G. A. Kim ◽  
H. J. Oh ◽  
M. J. Kim ◽  
Y. K. Jo ◽  
E. M. N. Setyawan ◽  
...  
Keyword(s):  
Telomere Length ◽  
Donor Cell ◽  
Telomerase Activity ◽  
Physiological Age ◽  
Biological Aging ◽  
Amplification Protocol ◽  
Donor Cells ◽  
Activity Measurements ◽  
Natural Breeding

Telomerase is important ribonucleoprotein for restoring telomere length from its own RNA template. Regarding cloned animals derived from somatic cell nuclear transfer (SCNT), interesting questions have been raised about whether the cloning process restores cellular telomerase activity undergone by their donor cells. The present study was conducted to determine the effects of cloning on telomerase activity in the dog and normality of telomerase activity in cloned dogs. Focusing our attention on differences in telomerase activity depending on the age, we analysed telomerase activity in dogs produced by natural breeding of various ages. Comparison of the telomerase activities of cloned dogs and those of dogs produced by natural breeding was also performed. For SCNT, 2 cell donors, 7- and 9-year-old beagles, were used and donor cells were isolated from ear skin. After establishing donor cell lines, the enucleated canine in vivo-matured oocytes and the cells were injected and fused by electrofusion. After 30 days from embryo transfer, pregnancy diagnosis was performed and 7 cloned dogs were produced on the due date. For standardization of telomerase activity in beagles produced by natural breeding, blood of total 14 dogs at each age (10 months, 20 months, 5, 7, and 8 years old) were collected and telomerase activity was measured by the telomeric repeat amplification protocol (TRAP) assay. Telomerase activity measurements of at least 6 replications in each dog were performed. For statistical analysis, one-way ANOVA with Dunn's Multiple Comparison Test was used. Significant differences in telomerase activity were observed between the blood of cloned and donor dogs. It was shown that mean telomerase activities were decreased according to biological aging with significances. Mean telomerase activities in 10 cloned dogs were higher than those of a donor dog. Cloned dogs also showed similar levels of telomerase activities as their age-matched natural bred dogs, suggesting that they are within the variation in normal dogs. These observations indicate that the cloning process restores the telomerase activity in the dog. Thus, complex regulation of telomerase activity during nuclear reprogramming may regulate and be involved in telomerase activity in cloned dogs. It remains to be determined whether telomere length is correlated with telomerase activity and if it accurately reflects the physiological age of cloned dogs.This study was supported by IPET (#311062–04–2-SB010), RDA (PJ008975022013), Research Institute for Veterinary Science, the BK21 program, Nestle Purina Korea, and TS Corporation.

scholarly journals Updated Understanding of Cancer as a Metabolic and Telomere-Driven Disease, and Proposal for Complex Personalized Treatment, a Hypothesis

2020 ◽  
Vol 21 (18) ◽  
pp. 6521
Author(s):  
Cristian Muresanu ◽  
Siva G. Somasundaram ◽  
Sergey V. Vissarionov ◽  
Luis Fernando Torres Solis ◽  
Arturo Solís Herrera ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Dna Damage ◽  
Telomere Length ◽  
Oxidative Dna Damage ◽  
Nuclear Gene ◽  
Holistic Approach ◽  
Telomerase Activity ◽  
Metabolic Reprogramming ◽  
Intermittent Fasting ◽  
Nuclear Gene Expression

In this review, we propose a holistic approach to understanding cancer as a metabolic disease. Our search for relevant studies in medical databases concludes that cancer cells do not evolve directly from normal healthy cells. We hypothesize that aberrant DNA damage accumulates over time—avoiding the natural DNA controls that otherwise repair or replace the rapidly replicating cells. DNA damage starts to accumulate in non-replicating cells, leading to senescence and aging. DNA damage is linked with genetic and epigenetic factors, but the development of cancer is favored by telomerase activity. Evidence indicates that telomere length is affected by chronic inflammations, alterations of mitochondrial DNA, and various environmental factors. Emotional stress also influences telomere length. Chronic inflammation can cause oxidative DNA damage. Oxidative stress, in turn, can trigger mitochondrial changes, which ultimately alter nuclear gene expression. This vicious cycle has led several scientists to view cancer as a metabolic disease. We have proposed complex personalized treatments that seek to correct multiple changes simultaneously using a psychological approach to reduce chronic stress, immune checkpoint therapy with reduced doses of chemo and radiotherapy, minimal surgical intervention, if any, and mitochondrial metabolic reprogramming protocols supplemented by intermittent fasting and personalized dietary plans without interfering with the other therapies.

scholarly journals In Barrett’s epithelial cells, weakly acidic bile salt solutions cause oxidative DNA damage with response and repair mediated by p38

2020 ◽  
Vol 318 (3) ◽  
pp. G464-G478
Author(s):  
Xiaofang Huo ◽  
Kerry B. Dunbar ◽  
Xi Zhang ◽  
Qiuyang Zhang ◽  
Stuart Jon Spechler ◽  
...  
Keyword(s):  
Dna Damage ◽  
Bile Salt ◽  
Barrett’S Esophagus ◽  
Esophageal Adenocarcinoma ◽  
Dna Damage Response ◽  
Barrett's Esophagus ◽  
Oxidative Dna Damage ◽  
Damage Response ◽  
Barrett's Metaplasia ◽  
Barrett’S Metaplasia

The frequency of esophageal adenocarcinoma is rising despite widespread use of proton pump inhibitors (PPIs), which heal reflux esophagitis but do not prevent reflux of weakly acidic gastric juice and bile in Barrett’s esophagus patients. We aimed to determine if weakly acidic (pH 5.5) bile salt medium (WABM) causes DNA damage in Barrett’s cells. Because p53 is inactivated frequently in Barrett’s esophagus and p38 can assume p53 functions, we explored p38’s role in DNA damage response and repair. We exposed Barrett’s cells with or without p53 knockdown to WABM, and evaluated DNA damage, its response and repair, and whether these effects are p38 dependent. We also measured phospho-p38 in biopsies of Barrett’s metaplasia exposed to deoxycholic acid (DCA). WABM caused phospho-H2AX increases that were blocked by a reactive oxygen species (ROS) scavenger. WABM increased phospho-p38 and reduced bromodeoxyuridine incorporation (an index of S phase entry). Repair of WABM-induced DNA damage proceeded through p38-mediated base excision repair (BER) associated with reduction-oxidation factor 1-apurinic/apyrimidinic endonuclease I (Ref-1/APE1). Cells treated with WABM supplemented with ursodeoxycholic acid (UDCA) exhibited enhanced p38-mediated responses to DNA damage. All of these effects were observed in p53-intact and p53-deficient Barrett’s cells. In patients, esophageal DCA perfusion significantly increased phospho-p38 in Barrett’s metaplasia. WABM exposure generates ROS, causing oxidative DNA damage in Barrett’s cells, a mechanism possibly underlying the rising frequency of esophageal adenocarcinoma despite PPI usage. p38 plays a central role in oxidative DNA damage response and Ref-1/APE1-associated BER, suggesting potential chemopreventive roles for agents like UDCA that increase p38 activity in Barrett’s esophagus. NEW & NOTEWORTHY We found that weakly acidic bile salt solutions, with compositions similar to the refluxed gastric juice of gastroesophageal reflux disease patients on proton pump inhibitors, cause oxidative DNA damage in Barrett’s metaplasia that could contribute to the development of esophageal adenocarcinoma. We also have elucidated a critical role for p38 in Barrett’s metaplasia in its response to and repair of oxidative DNA damage, suggesting a potential chemopreventive role for agents like ursodeoxycholic acid that increase p38 activity in Barrett’s esophagus.

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