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Telomere and telomerase

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https://www.readbyqxmd.com/read/29331736/dysfunctional-telomeres-and-hematological-disorders
#1
REVIEW
Elena Fiorini, Andrea Santoni, Simona Colla
Telomere biology disorders, which are characterized by telomerase activity haploinsufficiency and accelerated telomere shortening, most commonly manifest as degenerative diseases. Tissues with high rates of cell turnover, such as those in the hematopoietic system, are particularly vulnerable to defects in telomere maintenance genes that eventually culminate in bone marrow (BM) failure syndromes, in which the BM cannot produce sufficient new blood cells. Here, we review how telomere defects induce degenerative phenotypes across multiple organs, with particular focus on how they impact the hematopoietic stem and progenitor compartment and affect hematopoietic stem cell (HSC) self-renewal and differentiation...
January 4, 2018: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/29329057/chronic-corticosterone-induced-depression-mediates-premature-aging-in-rats
#2
Xiaoxian Xie, Qichen Shen, Lingyan Ma, Yangyang Chen, Binggong Zhao, Zhengwei Fu
BACKGROUND: Stress hormones such as corticosterone (CORT) play an essential role in the development of depression. Chronic CORT administration has been shown to induce dysfunction in the hypothalamic-pituitary-adrenal axis leading to depression, which was in turn associated with accelerated aging. However, the effect of CORT administration on aging remains unclear. METHODS: Rats were acclimatized for 1 week and then injected daily with CORT (40mg/kg) or vehicle (n = 10 each) for 21 consecutive days...
January 2, 2018: Journal of Affective Disorders
https://www.readbyqxmd.com/read/29324774/activated-carbon-n-acetylcysteine-microcapsule-protects-against-nonalcoholic-fatty-liver-disease-in-young-rats-via-activating-telomerase-and-inhibiting-apoptosis
#3
Tingting Shi, Xingxin Yang, Hongping Zhou, Jianjun Xi, Jingjing Sun, Yunling Ke, Jiankang Zhang, Yidan Shao, Xiaojie Jiang, Xuwang Pan, Shourong Liu, Rangxiao Zhuang
Non-alcoholic fatty liver disease (NAFLD) is becoming one of the world's most common chronic liver diseases in childhood, yet no therapy is available that has been approved by the food and drug administration (FDA). Previous studies have reported that telomere and telomerase are involved the development and progression of NAFLD. This study was designed to investigate the potential beneficial effects of activated carbon N-acetylcysteine (ACNAC) microcapsules on the development of NAFLD in young rats as well as the underlying mechanism(s) involved...
2018: PloS One
https://www.readbyqxmd.com/read/29312603/intratumoral-heterogeneity-and-tert-promoter-mutations-in-progressive-higher-grade-meningiomas
#4
Tareq A Juratli, Christian Thiede, Mara V A Koerner, Shilpa S Tummala, Dirk Daubner, Ganesh M Shankar, Erik A Williams, Maria Martinez-Lage, Silke Soucek, Katja Robel, Tristan Penson, Mechthild Krause, Steffen Appold, Matthias Meinhardt, Thomas Pinzer, Julie J Miller, Dietmar Krex, Heather A Ely, Ian M Silverman, Jason Christiansen, Gabriele Schackert, Hiroaki Wakimoto, Matthias Kirsch, Priscilla K Brastianos, Daniel P Cahill
Background: Recent studies have reported mutations in the telomerase reverse transcriptase promoter (TERTp) in meningiomas. We sought to determine the frequency, clonality and clinical significance of telomere gene alterations in a cohort of patients with progressive/higher-grade meningiomas. Methods: We characterized 64 temporally- and regionally-distinct specimens from 26 WHO grade III meningioma patients. On initial diagnoses, the meningiomas spanned all WHO grades (3 grade I, 13 grade II and 10 grade III)...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29305654/spontaneous-regression-of-neuroblastoma
#5
REVIEW
Garrett M Brodeur
Neuroblastomas are characterized by heterogeneous clinical behavior, from spontaneous regression or differentiation into a benign ganglioneuroma, to relentless progression despite aggressive, multimodality therapy. Indeed, neuroblastoma is unique among human cancers in terms of its propensity to undergo spontaneous regression. The strongest evidence for this comes from the mass screening studies conducted in Japan, North America and Europe and it is most evident in infants with stage 4S disease. This propensity is associated with a pattern of genomic change characterized by whole chromosome gains rather than segmental chromosome changes but the mechanism(s) underlying spontaneous regression are currently a matter of speculation...
January 5, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29305433/pinx1-and-tert-are-required-for-tnf-%C3%AE-induced-airway-smooth-muscle-chemokine-gene-expression
#6
Karl Deacon, Alan J Knox
Airway smooth muscle (ASM) cells contribute to asthmatic lung pathology with chemokine hypersecretion and increased ASM cell mass. With little recent progress in the development of asthma therapies, a greater understanding of lung inflammation mechanisms has become a priority. Chemokine gene expression in ASM cells is dependent upon NF-κB transcription factor activity. The telomerase/shelterin complex maintains chromosomal telomere ends during cell division. Telomerase is a possible cofactor for NF-κB activity, but its role in NF-κB activity in airway tissue inflammation is not known...
January 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29298360/chromosome-passenger-complex-is-required-for-the-survival-of-cells-with-ring-chromosomes-in-fission-yeast
#7
Ahmed G K Habib, Kanako Sugiura, Masaru Ueno
Ring chromosomes are circular chromosomal abnormalities that have been reported in association with some genetic disorders and cancers. In Schizosaccharomyces pombe, lack of function of protection of telomere 1 (Pot1) or telomerase catalytic subunit (Trt1) results in survivors with circular chromosomes. Hitherto, it is poorly understood how cells with circular chromosomes survive and how circular chromosomes are maintained. Fission yeast Cut17/Bir1, Ark1, Pic1, and Nbl1 is a conserved chromosome passenger complex (CPC) functioning mainly throughout mitosis...
2018: PloS One
https://www.readbyqxmd.com/read/29296896/maintenance-of-telomere-length-in-aml
#8
REVIEW
Peter M Lansdorp
The importance of telomere length to human health, aging, and cancer continues to be underappreciated. This review examines some basics of telomere biology and relates how telomere function, telomerase activity, and mutations in TERC or TERT are involved in bone marrow failure, leukemias, and other cancers. Given the challenge to obtain accurate data on telomerase activity and telomere length in specific cell types, the situation in acute myeloid leukemia (AML) remains puzzling. In most cancers, telomerase levels are increased after cells have encountered a "telomere crisis," which is typically associated with poor prognosis...
November 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29290468/stabilization-of-reversed-replication-forks-by-telomerase-drives-telomere-catastrophe
#9
Pol Margalef, Panagiotis Kotsantis, Valerie Borel, Roberto Bellelli, Stephanie Panier, Simon J Boulton
Telomere maintenance critically depends on the distinct activities of telomerase, which adds telomeric repeats to solve the end replication problem, and RTEL1, which dismantles DNA secondary structures at telomeres to facilitate replisome progression. Here, we establish that reversed replication forks are a pathological substrate for telomerase and the source of telomere catastrophe in Rtel1-/- cells. Inhibiting telomerase recruitment to telomeres, but not its activity, or blocking replication fork reversal through PARP1 inhibition or depleting UBC13 or ZRANB3 prevents the rapid accumulation of dysfunctional telomeres in RTEL1-deficient cells...
December 27, 2017: Cell
https://www.readbyqxmd.com/read/29290466/structural-insights-into-yeast-telomerase-recruitment-to-telomeres
#10
Hongwen Chen, Jing Xue, Dmitri Churikov, Evan P Hass, Shaohua Shi, Laramie D Lemon, Pierre Luciano, Alison A Bertuch, David C Zappulla, Vincent Géli, Jian Wu, Ming Lei
Telomerase maintains chromosome ends from humans to yeasts. Recruitment of yeast telomerase to telomeres occurs through its Ku and Est1 subunits via independent interactions with telomerase RNA (TLC1) and telomeric proteins Sir4 and Cdc13, respectively. However, the structures of the molecules comprising these telomerase-recruiting pathways remain unknown. Here, we report crystal structures of the Ku heterodimer and Est1 complexed with their key binding partners. Two major findings are as follows: (1) Ku specifically binds to telomerase RNA in a distinct, yet related, manner to how it binds DNA; and (2) Est1 employs two separate pockets to bind distinct motifs of Cdc13...
December 27, 2017: Cell
https://www.readbyqxmd.com/read/29290038/tight-co-twin-similarity-of-monozygotic-twins-for-htert-protein-level-of-t-cell-subsets-for-telomere-length-and-mitochondrial-dna-copy-number-but-not-for-telomerase-activity
#11
Dóra Melicher, Anett Illés, Éva Pállinger, Árpád Ferenc Kovács, Levente Littvay, Ádám Domonkos Tárnoki, Dávid László Tárnoki, András Bikov, Mária Judit Molnár, Edit Irén Buzás, András Falus
Our study analyzed lymphocyte subpopulations of 32 monozygotic twins and compared the level of the catalytic reverse transcriptase protein subunit (hTERT) in T lymphocytes (Tly), helper- (Th), cytotoxic- (Tc) and regulatory T cell (Treg) subgroups. Four variables related to telomere and mitochondrial biology were simultaneously assessed, applying multi-parametric flow cytometry, TRAP-ELISA assay and qPCR standard curve method on peripheral blood mononuclear cell (PBMC) samples of genetically matched individuals...
December 30, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29288666/zeb1-stimulates-breast-cancer-growth-by-up-regulating-htert-expression
#12
Pan Yu, Xi Shen, Wen Yang, Yunke Zhang, Chunping Liu, Tao Huang
Dysfunctional cell proliferation and death are the foundation of the malignant biological characteristics of cancers. In this study, we discovered that ZEB1 was positively correlated with hTERT in breast invasive ductal carcinoma samples at both the mRNA and protein levels. Further, our in vitro study in breast cancer cell lines confirmed that ZEB1 regulates hTERT expression at the mRNA and protein levels; thus, hTERT promotes or inhibits telomerase activity, and telomere length is either protected or reduced...
December 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29281671/short-telomere-length-in-ipf-lung-associates-with-fibrotic-lesions-and-predicts-survival
#13
Reinier Snetselaar, Aernoud A van Batenburg, Matthijs F M van Oosterhout, Karin M Kazemier, Suzan M Roothaan, Ton Peeters, Joanne J van der Vis, Roel Goldschmeding, Jan C Grutters, Coline H M van Moorsel
Telomere maintenance dysfunction has been implicated in the pathogenesis of Idiopathic Pulmonary Fibrosis (IPF). However, the mechanism of how telomere length is related to fibrosis in the lungs is unknown. Surgical lung biopsies of IPF patients typically show a heterogeneous pattern of non-fibrotic and fibrotic areas. Therefore, telomere length (TL) in both lung areas of patients with IPF and familial interstitial pneumonia was compared, specifically in alveolar type 2 (AT2) cells. Fluorescent in situ hybridization was used to determine TL in non-fibrotic and fibrotic areas of 35 subjects...
2017: PloS One
https://www.readbyqxmd.com/read/29274896/impact-of-oxidative-stress-on-telomere-biology
#14
REVIEW
Wareed Ahmed, Joachim Lingner
Telomere integrity is essential for genome stability and it regulates cell proliferation and tissue renewal. Several lines of evidence indicate that telomeres are particularly sensitive to oxidative damage. Moreover, recent studies demonstrate striking inhibitory effects of oxidative damage on telomerase activity. On the other hand, several mechanisms have been uncovered that either counteract oxidative damage at telomeres or remove the modified lesions. Here, we review the current understanding of oxidative damage and protection of telomeric DNA...
December 14, 2017: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/29273061/diagnosis-and-treatment-of-alt-tumors-is-trabectedin-a-new-therapeutic-option
#15
REVIEW
Luca Pompili, Carlo Leonetti, Annamaria Biroccio, Erica Salvati
Telomeres are specialized nucleoprotein structures responsible for protecting chromosome ends in order to prevent the loss of genomic information. Telomere maintenance is required for achieving immortality by neoplastic cells. While most cancer cells rely on telomerase re-activation for linear chromosome maintenance and sustained proliferation, a significant population of cancers (10-15%) employs telomerase-independent strategies, collectively referred to as Alternative Lengthening of Telomeres (ALT). ALT mechanisms involve different types of homology-directed telomere recombination and synthesis...
December 22, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29241838/telomerase-level-increase-is-related-to-n-3-polyunsaturated-fatty-acid-efficacy-in-first-episode-schizophrenia-secondary-outcome-analysis-of-the-offer-randomized-clinical-trial
#16
Tomasz Pawełczyk, Marta Grancow-Grabka, Elżbieta Trafalska, Janusz Szemraj, Natalia Żurner, Agnieszka Pawełczyk
Schizophrenia is associated with shortening of the lifespan mainly due to cardiovascular events, cancer and chronic obstructive pulmonary disease. Both telomere attrition and decrease of telomerase levels were observed in schizophrenia. Polyunsaturated fatty acids (PUFA) influence multiple biochemical mechanisms which are postulated to accelerate telomere shortening and limit the longevity of patients with schizophrenia. Intervention studies based on add-on therapy with n-3 polyunsaturated fatty acids (n-3 PUFA) in patients with schizophrenia did not assess the changes in telomerase levels...
December 11, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29238750/biomarkers-of-aging-associated-with-past-treatments-in-breast-cancer-survivors
#17
Zorica Scuric, Judith E Carroll, Julienne E Bower, Sam Ramos-Perlberg, Laura Petersen, Stephanie Esquivel, Matt Hogan, Aaron M Chapman, Michael R Irwin, Elizabeth C Breen, Patricia A Ganz, Robert Schiestl
Radiation and chemotherapy are effective treatments for cancer, but are also toxic to healthy cells. Little is known about whether prior exposure to these treatments is related to markers of cellular aging years later in breast cancer survivors. We examined whether past exposure to chemotherapy and/or radiation treatment was associated with DNA damage, telomerase activity, and telomere length 3-6 years after completion of primary treatments in breast cancer survivors (stage 0-IIIA breast cancer at diagnosis)...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29230030/silica-inhalation-altered-telomere-length-and-gene-expression-of-telomere-regulatory-proteins-in-lung-tissue-of-rats
#18
Mohammad Shoeb, Pius Joseph, Vamsi Kodali, Gul Mustafa, Breanne Y Farris, Christina Umbright, Jenny R Roberts, Aaron Erdely, James M Antonini
Exposure to silica can cause lung fibrosis and cancer. Identification of molecular targets is important for the intervention and/or prevention of silica-induced lung diseases. Telomeres consist of tandem repeats of DNA sequences at the end of chromosomes, preventing chromosomal fusion and degradation. Regulator of telomere length-1 (RTEL1) and telomerase reverse transcriptase (TERT), genes involved in telomere regulation and function, play important roles in maintaining telomere integrity and length. The goal of this study was to assess the effect of silica inhalation on telomere length and the regulation of RTEL1 and TERT...
December 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29229290/simple-detection-of-telomere-fusions-in-pancreatic-cancer-intraductal-papillary-mucinous-neoplasm-and-pancreatic-cyst-fluid
#19
Tatsuo Hata, Marco Dal Molin, Anne McGregor-Das, Tae Jun Song, Christopher Wolfgang, James R Eshleman, Ralph H Hruban, Michael Goggins
Telomere end-to-end fusions are an important source of chromosomal instability that arise in cells with critically shortened telomeres. We developed a nested real-time quantitative PCR method for telomere fusion detection in pancreatic ductal adenocarcinomas, intraductal papillary mucinous neoplasms (IPMNs), and IPMN cyst fluids. Ninety-one pancreatic cancer cell lines and xenograft samples, 93 IPMNs, and 93 surgically aspirated IPMN cyst fluid samples were analyzed. The association between telomere shortening, telomerase activity, and telomere fusion detection was evaluated...
December 6, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/29228317/leukocyte-telomere-length-at-birth-and-during-the-early-life-of-hiv-exposed-uninfected-children-following-in-utero-exposure-to-antiretrovirals
#20
Abhinav Ajaykumar, Hugo Soudeyns, Fatima Kakkar, Jason Brophy, Ari Bitnun, Ariane Alimenti, Arianne Y K Albert, Deborah M Money, Hélène C F Côté
Background: Maternal combination antiretroviral therapy (cART) during pregnancy could impact the health of HIV-exposed uninfected (HEU) children, as some antiretrovirals cross the placenta and can inhibit telomerase. Our objective was to compare HEU and HIV-unexposed uninfected (HUU) leukocyte telomere length (LTL) at birth and in early life, and investigate any relationship with cART exposure. Methods: HEU and HUU children's blood LTL was compared cross-sectionally at birth, and during the first three years of life...
December 8, 2017: Journal of Infectious Diseases
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