scholarly journals NADPH Oxidase Overactivity Underlies Telomere Shortening in Human Atherosclerosis

2020 ◽  
Vol 21 (4) ◽  
pp. 1434 ◽  
Author(s):  
Álvaro Pejenaute ◽  
Adriana Cortés ◽  
Javier Marqués ◽  
Laura Montero ◽  
Óscar Beloqui ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Telomere Length ◽  
Surrogate Marker ◽  
Superoxide Production ◽  
Phagocytic Cells ◽  
Specific Expression ◽  
Telomere Shortening ◽  
Human Atherosclerosis ◽  
Asymptomatic Subjects

Telomere shortening and oxidative stress are involved in the pathogenesis of atherosclerosis. Different studies have shown that phagocytic NADPH oxidase is associated with this disease. This study aimed to investigate the association between phagocytic NADPH oxidase and telomere shortening in human atherosclerosis. To assess this potential association, telomere length and phagocytic NADPH oxidase activity were determined by PCR and chemiluminescence, respectively, in a population of asymptomatic subjects free of overt clinical atherosclerosis. We also measured serum 8-hydroxy-2-deoxyguanosine (8-OHdG) levels (an index of oxidative stress) and carotid intima-media thickness (IMT), a surrogate marker of atherosclerosis. After adjusting them for age and sex, telomere length inversely correlated (p < 0.05) with NADPH oxidase-mediated superoxide production, with 8-OHdG values, and with carotid IMT. Interestingly, the asymptomatic subjects with plaques have a lower telomere length (p < 0.05), and higher values of plasma 8-OHdG and superoxide production (p < 0.05). These data were confirmed in a second population in which patients with coronary artery disease showed lower telomere length and higher 8-OHdG and superoxide production than the asymptomatic subjects. In both studies, NADPH oxidase-dependent superoxide production in phagocytic cells was only due to the specific expression of the Nox2 isoform. In conclusion, these findings suggest that phagocytic NADPH oxidase may be involved in oxidative stress-mediated telomere shortening, and that this axis may be critically involved in human atherosclerosis.

scholarly journals Telomere Shortening and Psychiatric Disorders: A Systematic Review

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1423
Author(s):  
Pedro A. Pousa ◽  
Raquel M. Souza ◽  
Paulo Henrique M. Melo ◽  
Bernardo H. M. Correa ◽  
Tamires S. C. Mendonça ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Psychological Distress ◽  
Mental Disorders ◽  
Psychiatric Disorders ◽  
Telomere Length ◽  
Traumatic Stress ◽  
Molecular Mechanisms ◽  
Cochrane Library ◽  
Telomere Shortening ◽  
Anxiety Depression

Telomeres are aging biomarkers, as they shorten while cells undergo mitosis. The aim of this study was to evaluate whether psychiatric disorders marked by psychological distress lead to alterations to telomere length (TL), corroborating the hypothesis that mental disorders might have a deeper impact on our physiology and aging than it was previously thought. A systematic search of the literature using MeSH descriptors of psychological distress (“Traumatic Stress Disorder” or “Anxiety Disorder” or “depression”) and telomere length (“cellular senescence”, “oxidative stress” and “telomere”) was conducted on PubMed, Cochrane Library and ScienceDirect databases. A total of 56 studies (113,699 patients) measured the TL from individuals diagnosed with anxiety, depression and posttraumatic disorders and compared them with those from healthy subjects. Overall, TL negatively associates with distress-related mental disorders. The possible underlying molecular mechanisms that underly psychiatric diseases to telomere shortening include oxidative stress, inflammation and mitochondrial dysfunction linking. It is still unclear whether psychological distress is either a cause or a consequence of telomere shortening.

scholarly journals Oxidative Stress, Telomere Shortening, and Apoptosis Associated to Sarcopenia and Frailty in Patients with Multimorbidity

2020 ◽  
Vol 9 (8) ◽  
pp. 2669 ◽  
Author(s):  
Máximo Bernabeu-Wittel ◽  
Raquel Gómez-Díaz ◽  
Álvaro González-Molina ◽  
Sofía Vidal-Serrano ◽  
Jesús Díez-Manglano ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Telomere Length ◽  
Prospective Observational Study ◽  
Oxygen Species ◽  
Oxidative Stress Markers ◽  
Blood Leukocytes ◽  
Telomere Shortening ◽  
Blood Samples ◽  
Stress Markers ◽  
Total Antioxidant

Background: The presence of oxidative stress, telomere shortening, and apoptosis in polypathological patients (PP) with sarcopenia and frailty remains unknown. Methods: Multicentric prospective observational study in order to assess oxidative stress markers (catalase, glutathione reductase (GR), total antioxidant capacity to reactive oxygen species (TAC-ROS), and superoxide dismutase (SOD)), absolute telomere length (aTL), and apoptosis (DNA fragmentation) in peripheral blood samples of a hospital-based population of PP. Associations of these biomarkers to sarcopenia, frailty, functional status, and 12-month mortality were analyzed. Results: Of the 444 recruited patients, 97 (21.8%), 278 (62.6%), and 80 (18%) were sarcopenic, frail, or both, respectively. Oxidative stress markers (lower TAC-ROS and higher SOD) were significantly enhanced and aTL significantly shortened in patients with sarcopenia, frailty or both syndromes. No evidence of apoptosis was detected in blood leukocytes of any of the patients. Both oxidative stress markers (GR, p = 0.04) and telomere shortening (p = 0.001) were associated to death risk and to less survival days. Conclusions: Oxidative stress markers and telomere length were enhanced and shortened, respectively, in blood samples of polypathological patients with sarcopenia and/or frailty. Both were associated to decreased survival. They could be useful in the clinical practice to assess vulnerable populations with multimorbidity and of potential interest as therapeutic targets.

scholarly journals Histone Acetyltransferase-Dependent Pathways Mediate Upregulation of NADPH Oxidase 5 in Human Macrophages under Inflammatory Conditions: A Potential Mechanism of Reactive Oxygen Species Overproduction in Atherosclerosis

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Mihaela-Loredana Vlad ◽  
Simona-Adriana Manea ◽  
Alexandra-Gela Lazar ◽  
Monica Raicu ◽  
Horia Muresian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Histone Acetyltransferase ◽  
Gene Promoter ◽  
Epigenetic Mechanism ◽  
Human Macrophages ◽  
Inflammatory Conditions ◽  
Gene And Protein Expression ◽  
Human Atherosclerosis ◽  
Nadph Oxidase 5

Histone acetylation plays a major role in epigenetic regulation of gene expression. Monocyte-derived macrophages express functional NADPH oxidase 5 (Nox5) that contributes to oxidative stress in atherogenesis. The mechanisms of Nox5 regulation are not entirely elucidated. The aim of this study was to investigate the expression pattern of key histone acetyltransferase subtypes (p300, HAT1) in human atherosclerosis and to determine their role in mediating the upregulation of Nox5 in macrophages under inflammatory conditions. Human nonatherosclerotic and atherosclerotic tissue samples were collected in order to determine the expression of p300 and HAT1 isoforms, H3K27ac, and Nox5. In vitro determinations were done on human macrophages exposed to lipopolysaccharide in the absence or presence of histone acetyltransferase inhibitors. Western blot, immunohistochemistry, immunofluorescence, real-time PCR, transfection, and chromatin immunoprecipitation assay were employed. The protein levels of p300 and HAT1 isoforms, H3K27ac, and Nox5 were found significantly elevated in human atherosclerotic specimens. Immunohistochemistry/immunofluorescence staining revealed that p300, HAT1, H3K27ac, H3K9ac, and Nox5 proteins were colocalized in the area of CD45+/CD68+ immune cells and lipid-rich deposits within human atherosclerotic plaques. Lipopolysaccharide induced the levels of HAT1, H3K27ac, H3K9ac, and Nox5 and the recruitment of p300 and HAT1 at the sites of active transcription within Nox5 gene promoter in cultured human macrophages. Pharmacological inhibition of histone acetyltransferase significantly reduced the Nox5 gene and protein expression in lipopolysaccharide-challenged macrophages. The overexpression of p300 or HAT1 enhanced the Nox5 gene promoter activity. The histone acetyltransferase system is altered in human atherosclerosis. Under inflammatory conditions, HAT subtypes control Nox5 overexpression in cultured human macrophages. The data suggest the existence of a new epigenetic mechanism underlying oxidative stress in atherosclerosis.

scholarly journals Prenatal thyroid hormones accelerate postnatal growth and telomere shortening in wild great tits

2021 ◽  
Author(s):  
Bin-Yan Hsu ◽  
Nina Cossin-Sevrin ◽  
Antoine Stier ◽  
Suvi Ruuskanen
Keyword(s):  
Oxidative Stress ◽  
Thyroid Hormones ◽  
Telomere Length ◽  
Early Life ◽  
Later Life ◽  
Delayed Effect ◽  
Oxidative Stress Biomarkers ◽  
Term Survival ◽  
Telomere Shortening ◽  
The Impact

Early-life environment is known to affect later-life health and disease, which could be mediated by the early-life programming of telomere length, a key hallmark of ageing. According to the fetal programming of telomere biology hypothesis, variation in prenatal exposure to hormones is likely to influence telomere length. Yet the contribution of key metabolic hormones, i.e. thyroid hormones (THs), has been largely ignored. We recently showed that in contrast to predictions, exposure to elevated prenatal THs increased postnatal telomere length in wild collared flycatchers, but the generality of such effect, its underlying proximate mechanisms and consequences on survival have not been investigated. We therefore conducted a comprehensive study evaluating the impact of THs on potential drivers of telomere dynamics (growth, post-natal THs, mitochondria and oxidative stress), telomere length and medium-term survival using wild great tits as a model system. While prenatal THs did not significantly affect telomere length after hatching (i.e. day 7), they influenced postnatal telomere shortening (i.e. shorter telomeres at day 14 and the following winter) but not apparent survival. Circulating THs, mitochondrial density or oxidative stress biomarkers were not significantly influenced, whereas TH-supplemented group showed accelerated growth, which may explain the observed delayed effect on telomeres. We discuss several alternative hypotheses that may explain the contrast with our previous findings in flycatchers. Given that shorter telomeres in early life tend to be carried until adulthood and are often associated with decreased survival prospects, the effects of prenatal THs on telomeres may have long-lasting effects on senescence.

scholarly journals Telomere Length Shortening in Microglia: Implication for Accelerated Senescence and Neurocognitive Deficits in HIV

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 721
Author(s):  
Chiu-Bin Hsiao ◽  
Harneet Bedi ◽  
Raquel Gomez ◽  
Ayesha Khan ◽  
Taylor Meciszewski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Telomere Length ◽  
Mitochondrial Function ◽  
Immune Cells ◽  
Telomerase Activity ◽  
Microglial Cells ◽  
Neurocognitive Deficits ◽  
Telomere Shortening ◽  
Hiv Tat ◽  
Hiv 1

The widespread use of combination antiretroviral therapy (cART) has led to the accelerated aging of the HIV-infected population, and these patients continue to have a range of mild to moderate HIV-associated neurocognitive disorders (HAND). Infection results in altered mitochondrial function. The HIV-1 viral protein Tat significantly alters mtDNA content and enhances oxidative stress in immune cells. Microglia are the immune cells of the central nervous system (CNS) that exhibit a significant mitotic potential and are thus susceptible to telomere shortening. HIV disrupts the normal interplay between microglia and neurons, thereby inducing neurodegeneration. HIV cART contributes to the inhibition of telomerase activity and premature telomere shortening in activated peripheral blood mononuclear cells (PBMC). However, limited information is available on the effect of cART on telomere length (TL) in microglia. Although it is well established that telomere shortening induces cell senescence and contributes to the development of age-related neuro-pathologies, the effect of HIV-Tat on telomere length in human microglial cells and its potential contribution to HAND are not well understood. It is speculated that in HAND intrinsic molecular mechanisms that control energy production underlie microglia-mediated neuronal injury. TL, telomerase and mtDNA expression were quantified in microglial cells using real time PCR. Cellular energetics were measured using the Seahorse assay. The changes in mitochondrial function were examined by Raman Spectroscopy. We have also examined TL in the PBMC obtained from HIV-1 infected rapid progressors (RP) on cART and those who were cART naïve, and observed a significant decrease in telomere length in RP on cART as compared to RP’s who were cART naïve. We observed a significant decrease in telomerase activity, telomere length and mitochondrial function, and an increase in oxidative stress in human microglial cells treated with HIV Tat. Neurocognitive impairment in HIV disease may in part be due to accelerated neuro-pathogenesis in microglial cells, which is attributable to increased oxidative stress and mitochondrial dysfunction.

scholarly journals Oxidative Stress after Subarachnoid Hemorrhage in gp91phox Knockout Mice

2007 ◽  
Vol 34 (3) ◽  
pp. 356-361 ◽  
Author(s):  
Shimin Liu ◽  
Jiping Tang ◽  
Robert P Ostrowski ◽  
Elena Titova ◽  
Cara Monroe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Mortality Rate ◽  
Nadph Oxidase ◽  
Water Content ◽  
Knockout Mice ◽  
Early Brain Injury ◽  
Superoxide Production ◽  
Wild Type

Background:Oxidative stress largely contributes to early brain injury after subarachnoid hemorrhage (SAH). One of the major sources of reactive oxygen species is NADPH oxidase, upregulated after SAH. We hypothesized that NADPH oxidase-induced oxidative stress plays a major causative role in early brain injury after SAH.Methods:Using gp91phox knockout (ko) and wild-type (wt) mice, we studied early brain injury in the endovascular perforation model of SAH. Mortality rate, cerebral edema, oxidative stress, and superoxide production were measured at 24 h after SAH. Neurological evaluation was done at 23 h after SAH surgery.Results:Genotyping confirmed the existence of a nonfunctional gp91phox gene in the ko mice. CBF measurements did not show differences in SAH-induced acute ischemia between ko and wt mice. SAH caused a significant increase of water content in the ipsilateral hemisphere as well as an increase of Malondialdehyde (MDA) levels and superoxide production. There were no significant differences in post-SAH mortality rate, brain water content and the intensity of the oxidative stress between knockout and wild type groups of mice.Conclusions:Our results suggest that gp91phox is not critically important to the early brain injury after SAH. An adaptive compensatory mechanism for free radical production in knockout mice is discussed.

scholarly journals Accelerated telomere attrition in children and teenagers with α1-antitrypsin deficiency

2016 ◽  
Vol 48 (2) ◽  
pp. 350-358 ◽  
Author(s):  
Amparo Escribano ◽  
Sara Pastor ◽  
Ana Reula ◽  
Silvia Castillo ◽  
Silvia Vicente ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Risk ◽  
Telomere Length ◽  
Telomerase Activity ◽  
Multiple Hypothesis Testing ◽  
Intermediate Risk ◽  
Telomere Shortening ◽  
Telomere Attrition ◽  
Antitrypsin Deficiency ◽  
Risk Patients

Numerous studies have shown that oxidative stress accelerates telomere shortening in several lung pathologies. Since oxidative stress is involved in the pathophysiology of α1-antitrypsin deficiency (AATD), we hypothesised that telomere shortening would be accelerated in AATD patients. This study aimed to assess telomere length in AATD patients and to study its association with α1-antitrypsin phenotypes.Telomere length, telomerase activity, telomerase reverse transcriptase (hTERT) expression and biomarkers of oxidative stress were measured in 62 children and teenagers (aged 2–18 years) diagnosed with AATD and 18 controls (aged 3–16 years).Our results show that intermediate-risk (MZ; SZ) and high-risk (ZZ) AATD patients have significantly shorter telomeres and increased oxidative stress than controls. Correlation studies indicate that telomere length was related to oxidative stress markers in AATD patients. Multiple hypothesis testing revealed an association between telomere length, telomerase activity, hTERT expression and AATD phenotypes; high-risk patients showed shorter telomeres, lower hTERT expression and decreased telomerase activity than intermediate-risk and low-risk patients.AATD patients show evidence of increased oxidative stress leading to telomere attrition. An association between telomere and α1-antitrypsin phenotypes is observed suggesting that telomere length could be a promising biomarker for AATD disease progression.

Prognostic implications of differences in telomere length between normal and malignant cells from patients with chronic myeloid leukemia measured by flow cytometry

Blood ◽  
2000 ◽  
Vol 95 (6) ◽  
pp. 1883-1890 ◽  
Author(s):  
Tim H. Brümmendorf ◽  
Tessa L. Holyoake ◽  
Nathalie Rufer ◽  
Michael J. Barnett ◽  
Michael Schulzer ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Chronic Myeloid Leukemia ◽  
T Lymphocytes ◽  
Telomere Length ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Surrogate Marker ◽  
Chronic Phase ◽  
Telomere Shortening ◽  
Normal Individuals

Abstract Chronic myeloid leukemia (CML) is a clonal, multilineage myeloproliferative disorder characterized by the Philadelphia chromosome (Ph) and a marked expansion of myeloid cells. Previous studies have indicated that the telomere length in blood cells may indicate their replicative history. However, the large variation in telomere length between individuals complicates the use of this parameter in CML and other hematologic disorders. To circumvent this problem, we compared the telomere length in peripheral blood or bone marrow cells with purified normal (Ph−) T lymphocytes from the same CML patient using fluorescence in situ hybridization and flow cytometry. Overall telomere fluorescence was significantly reduced in Ph+ cells from patients with CML compared to blood leukocytes from normal individuals (P &lt; 0.001) or normal (Ph−) T lymphocytes from the same individuals (n = 51, P &lt; 0.001). Cells from patients in accelerated phase or blast phase (AP/BP) showed significantly shorter average telomere length than cells from patients in chronic phase (CP,P = 0.02) or cytogenetic remission (CR,P = 0.03). Patients in CP who subsequently developed BP within 2 years had significantly shorter telomeres than those who did not develop BP for at least 2 years (P &lt; 0.05). Accelerated replication-dependent telomere shortening in Ph+ versus Ph− leukocytes supports previous evidence that Ph+ stem cells cycle more actively than their counterparts in normal individuals. Our data further suggest that telomere shortening may serve as a surrogate marker of disease progression in patients with CP CML, supporting a mechanistic link between CML stem cell turnover, genetic instability, and malignant evolution in this disease. (Blood. 2000;95:1883-1890)

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