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Article ; Online: Integrated analysis of

Simón-Carrasco, Lucía / Pietrini, Elena / López-Contreras, Andrés J

2024 Volume 23, Issue 1, Page(s) 92–113

Abstract: The Fragile Histidine Triad Diadenosine Triphosphatase ( ...

Abstract	The Fragile Histidine Triad Diadenosine Triphosphatase (
MeSH term(s)	Humans ; Acid Anhydride Hydrolases/genetics ; Chromosome Fragile Sites ; Neoplasm Proteins/genetics ; Neoplasms/genetics
Chemical Substances	Acid Anhydride Hydrolases (EC 3.6.-) ; Neoplasm Proteins
Language	English
Publishing date	2024-01-18
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2146183-1
ISSN	1551-4005 ; 1538-4101 ; 1554-8627
ISSN (online)	1551-4005
ISSN	1538-4101 ; 1554-8627
DOI	10.1080/15384101.2024.2304509
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Article: ATRX, a guardian of chromatin.

Aguilera, Paula / López-Contreras, Andrés J

Trends in genetics : TIG

2023 Volume 39, Issue 6, Page(s) 505–519

Abstract: ATRX (alpha-thalassemia mental retardation X-linked) is one of the most frequently mutated tumor suppressor genes in human cancers, especially in glioma, and recent findings indicate roles for ATRX in key molecular pathways, such as the regulation of ... ...

Abstract	ATRX (alpha-thalassemia mental retardation X-linked) is one of the most frequently mutated tumor suppressor genes in human cancers, especially in glioma, and recent findings indicate roles for ATRX in key molecular pathways, such as the regulation of chromatin state, gene expression, and DNA damage repair, placing ATRX as a central player in the maintenance of genome stability and function. This has led to new perspectives about the functional role of ATRX and its relationship with cancer. Here, we provide an overview of ATRX interactions and molecular functions and discuss the consequences of its impairment, including alternative lengthening of telomeres and therapeutic vulnerabilities that may be exploited in cancer cells.
MeSH term(s)	Humans ; Chromatin/genetics ; DNA Helicases/genetics ; X-linked Nuclear Protein/genetics ; Telomere Homeostasis/genetics ; Glioma/genetics ; Telomere
Chemical Substances	Chromatin ; DNA Helicases (EC 3.6.4.-) ; X-linked Nuclear Protein (EC 3.6.4.12) ; ATRX protein, human (EC 3.6.4.12)
Language	English
Publishing date	2023-03-07
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	619240-3
ISSN	1362-4555 ; 0168-9525 ; 0168-9479
ISSN (online)	1362-4555
ISSN	0168-9525 ; 0168-9479
DOI	10.1016/j.tig.2023.02.009
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Article ; Online: PICH deficiency limits the progression of MYC-induced B-cell lymphoma.

Castejón-Griñán, María / Albers, Eliene / Simón-Carrasco, Lucía / Aguilera, Paula / Sbroggio, Mauro / Pladevall-Morera, David / Ingham, Andreas / Lim, Ernest / Guillen-Benitez, Alba / Pietrini, Elena / Lisby, Michael / Hickson, Ian D / Lopez-Contreras, Andres J

Blood cancer journal

2024 Volume 14, Issue 1, Page(s) 16

Abstract: Plk1-interacting checkpoint helicase (PICH) is a DNA translocase involved in resolving ultrafine anaphase DNA bridges and, therefore, is important to safeguard chromosome segregation and stability. PICH is overexpressed in various human cancers, ... ...

Abstract	Plk1-interacting checkpoint helicase (PICH) is a DNA translocase involved in resolving ultrafine anaphase DNA bridges and, therefore, is important to safeguard chromosome segregation and stability. PICH is overexpressed in various human cancers, particularly in lymphomas such as Burkitt lymphoma, which is caused by MYC translocations. To investigate the relevance of PICH in cancer development and progression, we have combined novel PICH-deficient mouse models with the Eμ-Myc transgenic mouse model, which recapitulates B-cell lymphoma development. We have observed that PICH deficiency delays the onset of MYC-induced lymphomas in Pich heterozygous females. Moreover, using a Pich conditional knockout mouse model, we have found that Pich deletion in adult mice improves the survival of Eμ-Myc transgenic mice. Notably, we show that Pich deletion in healthy adult mice is well tolerated, supporting PICH as a suitable target for anticancer therapies. Finally, we have corroborated these findings in two human Burkitt lymphoma cell lines and we have found that the death of cancer cells was accompanied by chromosomal instability. Based on these findings, we propose PICH as a potential therapeutic target for Burkitt lymphoma and for other cancers where PICH is overexpressed.
MeSH term(s)	Adult ; Female ; Animals ; Humans ; Mice ; Burkitt Lymphoma/genetics ; Cell Line ; Chromosomal Instability ; Disease Models, Animal ; Mice, Knockout ; Mice, Transgenic ; DNA
Chemical Substances	DNA (9007-49-2)
Language	English
Publishing date	2024-01-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2600560-8
ISSN	2044-5385 ; 2044-5385
ISSN (online)	2044-5385
ISSN	2044-5385
DOI	10.1038/s41408-024-00979-y
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Book ; Online: Signalling DNA Damage

Fernandez-Capetillo, Oscar / Lopez-Contreras, Andres Joaquin

2012

Abstract: ... DSB are used as repair intermediates during V(D)J and Class-Switch recombination (CSR) in lymphocytes ...

Abstract	During our lifetime, the genome is constantly being exposed to different types of damage caused either by exogenous sources (radiations and/or genotoxic compound) but also as byproducts of endogenous processes (reactive oxigen species during respiration, stalled forks during replication, eroded telomeres, etc). From a structural point of view, there are many types of DNA damage including single or double strand breaks, base modifications and losses or base-pair mismatches. The amount of lesions that we face is enormous with estimates suggesting that each of our 1013 cells has to deal with around 10.000 lesions per day [1]. While the majority of these events are properly resolved by specialized mechanisms, a deficient response to DNA damage, and particularly to DSB, harbors a serious threat to human health [2].DSB can be formed [1] following an exposure to ionizing radiation (X- or γ-rays) or clastogenic drugs; [2] endogenously, during DNA replication, or [3], as a consequence of reactive oxygen species (ROS) generated during oxidative metabolism. In addition, programmed DSB are used as repair intermediates during V(D)J and Class-Switch recombination (CSR) in lymphocytes [3], or during meiotic recombination [4]. Because of this, immunodeficiency and/or sterility problems are frequently associated with DDR-related pathologies
Keywords	Science (General)
Size	1 electronic resource ( p.)
Publisher	Intech
Document type	Book ; Online
Note	English ; Open Access
HBZ-ID	HT020101736
ISBN	9789535107378 ; 9535107372
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Dysregulated neutrophil extracellular traps formation in sepsis.

Mulet, Maria / Osuna-Gómez, Ruben / Zamora, Carlos / Artesero, Iris / Arús, Marc / Vera-Artazcoz, Paula / Cordón, Alejandra / Vilalta, Noelia / San-José, Paula / Abril, Andrés / Moliné, Antoni / Morán, Indalecio / López-Contreras, Joaquín / Vidal, Silvia

Immunology

2023 Volume 170, Issue 3, Page(s) 374–387

Abstract: The migration and antimicrobial functions of neutrophils seem to be impaired during sepsis and contribute to the dysregulation of immune responses and disease pathogenesis. However, the role of neutrophil extracellular traps (NETs) remains to be ... ...

Abstract	The migration and antimicrobial functions of neutrophils seem to be impaired during sepsis and contribute to the dysregulation of immune responses and disease pathogenesis. However, the role of neutrophil extracellular traps (NETs) remains to be clarified. The study aimed to analyse sequential phenotypic and functional changes of neutrophils during the time following the diagnosis of sepsis. We prospectively enrolled 49 septic and 18 non-septic patients from the intensive care unit (ICU) and emergency room (ER) and 20 healthy volunteers (HV). Baseline blood samples from septic and non-septic patients were collected within 12 h of admission to the hospital. Additional septic samples were drawn at 24, 48 and 72 h after baseline. Neutrophil phenotype and degranulation capacity were assessed by flow cytometry and NET formation was quantified by fluorescence. Neutrophils from septic patients exhibited increased CD66b, CD11b and CD177 expression but displayed reduced NET formation at baseline compared with non-septic patients and HV controls. Neutrophils expressing CD177 interacted less with platelets, were related to reduced NETosis and tended to indicate a worse sepsis outcome. In vitro experiments revealed that neutrophil function is compromised by the origin of sepsis, including the pathogen type and the affected organ. Assessing a decision tree model, our study showed that CD11b expression and NETosis values are useful variables to discriminate septic from non-septic patients. We conclude that sepsis induces changes in neutrophil phenotype and function that may compromise the effective capacity of the host to eliminate pathogens.
MeSH term(s)	Humans ; Extracellular Traps/metabolism ; Sepsis ; Neutrophils/metabolism ; Phenotype
Language	English
Publishing date	2023-06-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80124-0
ISSN	1365-2567 ; 0019-2805 ; 0953-4954
ISSN (online)	1365-2567
ISSN	0019-2805 ; 0953-4954
DOI	10.1111/imm.13676
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Article ; Online: New insights of polyamine metabolism in testicular physiology: A role of ornithine decarboxylase antizyme inhibitor 2 (AZIN2) in the modulation of testosterone levels and sperm motility.

Lambertos, Ana / Ramos-Molina, Bruno / López-Contreras, Andrés J / Cremades, Asunción / Peñafiel, Rafael

PloS one

2018 Volume 13, Issue 12, Page(s) e0209202

Abstract: The specific role of polyamines in the testis physiology is not fully understood. Antizymes (OAZs) and antizyme inhibitors (AZINs) are modulators of ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis and polyamine uptake. Although the ... ...

Abstract	The specific role of polyamines in the testis physiology is not fully understood. Antizymes (OAZs) and antizyme inhibitors (AZINs) are modulators of ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis and polyamine uptake. Although the three known OAZs are expressed in the testis, only OAZ3 is testis specific and has been proven to have an essential role in male fertility. Regarding the two existing AZINs, AZIN2 is the most abundantly expressed member in this gonad. Whereas previous studies suggested that AZIN2 might participate in mouse spermatogenesis, immunohistological analysis of human testicular sections revealed that AZIN2 is also detected in the steroidogenic Leydig cells but not in the germinal epithelium. In the present study, we found a close ontogenic similarity in the mRNA levels of OAZs and AZINs between mice and rats, but an opposite expression pattern of ODC activity. Further analysis of AZIN2 and OAZ3 in the testis of mice with different alterations in spermatogenesis and fertility, induced either genetically or pharmacologically, corroborated that both AZIN2 and OAZ3 are mainly expressed in the haploid germinal cells. Finally, by using transgenic mice with a truncated Azin2 gene fused to the bacterial lacZ gene, we studied the expression of Azin2 in testes, epididymides and spermatozoa. AZIN2 was detected in spermatids and spermatozoa, as well as in Leydig cells, and in epithelial epidydimal cells. Azin2 knock-out male mice were fertile; however, they showed marked decreases in testicular putrescine and plasma and testicular testosterone levels, and a dramatic reduction in the sperm motility. These results suggest an important role for AZIN2 in testicular cells by modulating polyamine concentrations, testosterone synthesis and sperm function. Overall, our data corroborate the relevance of polyamine regulation in testis functions, where both AZIN2 and OAZ3 play fundamental roles.
MeSH term(s)	Animals ; Carrier Proteins/metabolism ; Chorionic Gonadotropin/administration & dosage ; Chorionic Gonadotropin/metabolism ; Epididymis/enzymology ; Epididymis/growth & development ; Epithelial Cells/enzymology ; Gene Expression ; Humans ; Male ; Mice, Inbred C57BL ; Mice, Transgenic ; Neoplasms, Germ Cell and Embryonal/metabolism ; Polyamines/metabolism ; Rats, Sprague-Dawley ; Sperm Motility/physiology ; Spermatozoa/metabolism ; Testicular Neoplasms/metabolism ; Testis/enzymology ; Testis/growth & development ; Testosterone/metabolism
Chemical Substances	Carrier Proteins ; Chorionic Gonadotropin ; Polyamines ; Testosterone (3XMK78S47O)
Language	English
Publishing date	2018-12-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0209202
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Article ; Online: Supraphysiological protection from replication stress does not extend mammalian lifespan.

Albers, Eliene / Avram, Alexandra / Sbroggio, Mauro / Fernandez-Capetillo, Oscar / Lopez-Contreras, Andres J

Aging

2020 Volume 12, Issue 7, Page(s) 5612–5624

Abstract: Replication Stress (RS) is a type of DNA damage generated at the replication fork, characterized by single-stranded DNA (ssDNA) accumulation, and which can be caused by a variety of factors. Previous studies have reported elevated RS levels in aged cells. ...

Abstract	Replication Stress (RS) is a type of DNA damage generated at the replication fork, characterized by single-stranded DNA (ssDNA) accumulation, and which can be caused by a variety of factors. Previous studies have reported elevated RS levels in aged cells. In addition, mouse models with a deficient RS response show accelerated aging. However, the relevance of endogenous or physiological RS, compared to other sources of genomic instability, for the normal onset of aging is unknown. We have performed long term survival studies of transgenic mice with extra copies of the
MeSH term(s)	Animals ; Checkpoint Kinase 1/genetics ; Checkpoint Kinase 1/metabolism ; DNA Damage ; DNA Replication ; Longevity/genetics ; Mice ; Mice, Transgenic ; Ribonucleoside Diphosphate Reductase/genetics ; Ribonucleoside Diphosphate Reductase/metabolism
Chemical Substances	ribonucleotide reductase M2 (EC 1.17.4.-) ; Ribonucleoside Diphosphate Reductase (EC 1.17.4.1) ; Checkpoint Kinase 1 (EC 2.7.11.1) ; Chek1 protein, mouse (EC 2.7.11.1)
Language	English
Publishing date	2020-04-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.103039
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Article: ATRX-Deficient High-Grade Glioma Cells Exhibit Increased Sensitivity to RTK and PDGFR Inhibitors.

Pladevall-Morera, David / Castejón-Griñán, María / Aguilera, Paula / Gaardahl, Karina / Ingham, Andreas / Brosnan-Cashman, Jacqueline A / Meeker, Alan K / Lopez-Contreras, Andres J

Cancers

2022 Volume 14, Issue 7

Abstract: High-grade glioma, including anaplastic astrocytoma and glioblastoma (GBM) patients, have a poor prognosis due to the lack of effective treatments. Therefore, the development of new therapeutic strategies to treat these gliomas is urgently required. ... ...

Abstract	High-grade glioma, including anaplastic astrocytoma and glioblastoma (GBM) patients, have a poor prognosis due to the lack of effective treatments. Therefore, the development of new therapeutic strategies to treat these gliomas is urgently required. Given that high-grade gliomas frequently harbor mutations in the SNF2 family chromatin remodeler
Language	English
Publishing date	2022-03-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14071790
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Article: The mouse Gm853 gene encodes a novel enzyme: Leucine decarboxylase.

Lambertos, Ana / Ramos-Molina, Bruno / Cerezo, David / López-Contreras, Andrés J / Peñafiel, Rafael

Biochimica et biophysica acta. General subjects

2017 Volume 1862, Issue 3, Page(s) 365–376

Abstract: Ornithine decarboxylase (ODC) is a key enzyme in the biosynthesis of polyamines. ODC-antizyme inhibitors (AZINs) are homologous proteins of ODC, devoid of enzymatic activity but acting as regulators of polyamine levels. The last paralogue gene recently ... ...

Abstract	Ornithine decarboxylase (ODC) is a key enzyme in the biosynthesis of polyamines. ODC-antizyme inhibitors (AZINs) are homologous proteins of ODC, devoid of enzymatic activity but acting as regulators of polyamine levels. The last paralogue gene recently incorporated into the ODC/AZINs family is the murine Gm853, which is located in the same chromosome as AZIN2, and whose biochemical function is still unknown. By means of transfection assays of HEK293T cells with a plasmid containing the coding region of Gm853, we show here that unlike ODC, GM853 was a stable protein that was not able to decarboxylate l-ornithine or l-lysine and that did not act as an antizyme inhibitor. However, GM853 showed leucine decarboxylase activity, an enzymatic activity never described in animal cells, and by acting on l-leucine (Km=7.03×10
MeSH term(s)	Amino Acid Sequence ; Amino Acids/metabolism ; Animals ; Carboxy-Lyases ; Enzyme Induction/drug effects ; Female ; HEK293 Cells ; Humans ; Kidney/enzymology ; Male ; Mice ; Mice, Inbred C57BL ; Ornithine Decarboxylase/metabolism ; Recombinant Proteins/metabolism ; Sequence Alignment ; Sequence Homology, Amino Acid ; Substrate Specificity ; Testosterone Propionate/pharmacology ; Transfection
Chemical Substances	Amino Acids ; Recombinant Proteins ; Carboxy-Lyases (EC 4.1.1.-) ; Gm853 protein, mouse (EC 4.1.1.-) ; Ornithine Decarboxylase (EC 4.1.1.17) ; Testosterone Propionate (WI93Z9138A)
Language	English
Publishing date	2017-11-04
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0304-4165 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0304-4165 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbagen.2017.11.007
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Article ; Online: Social Inequalities in Mental Health and Self-Perceived Health in the First Wave of COVID-19 Lockdown in Latin America and Spain: Results of an Online Observational Study.

Salas Quijada, Carmen / López-Contreras, Natalia / López-Jiménez, Tomás / Medina-Perucha, Laura / León-Gómez, Brenda Biaani / Peralta, Andrés / Arteaga-Contreras, Karen M / Berenguera, Anna / Queiroga Gonçalves, Alessandra / Horna-Campos, Olivia Janett / Mazzei, Marinella / Anigstein, Maria Sol / Ribeiro Barbosa, Jakeline / Bardales-Mendoza, Olga / Benach, Joan / Borges Machado, Daiane / Torres Castillo, Ana Lucía / Jacques-Aviñó, Constanza

International journal of environmental research and public health

2023 Volume 20, Issue 9

Abstract: COVID-19 lockdowns greatly affected the mental health of populations and collectives. This study compares the mental health and self-perceived health in five countries of Latin America and Spain, during the first wave of COVID 19 lockdown, according to ... ...

Abstract	COVID-19 lockdowns greatly affected the mental health of populations and collectives. This study compares the mental health and self-perceived health in five countries of Latin America and Spain, during the first wave of COVID 19 lockdown, according to social axes of inequality. This was a cross-sectional study using an online, self-managed survey in Brazil, Chile, Ecuador, Mexico, Peru, and Spain. Self-perceived health (SPH), anxiety (measured through GAD-7) and depression (measured through PHQ-9) were measured along with lockdown, COVID-19, and social variables. The prevalence of poor SPH, anxiety, and depression was calculated. The analyses were stratified by gender (men = M; women = W) and country. The data from 39,006 people were analyzed (W = 71.9%). There was a higher prevalence of poor SPH and bad mental health in women in all countries studied. Peru had the worst SPH results, while Chile and Ecuador had the worst mental health indicators. Spain had the lowest prevalence of poor SPH and mental health. The prevalence of anxiety and depression decreased as age increased. Unemployment, poor working conditions, inadequate housing, and the highest unpaid workload were associated with worse mental health and poor SPH, especially in women. In future policies, worldwide public measures should consider the great social inequalities in health present between and within countries in order to tackle health emergencies while reducing the health breach between populations.
MeSH term(s)	Male ; Humans ; Female ; COVID-19/epidemiology ; COVID-19/psychology ; Mental Health ; Latin America/epidemiology ; Spain/epidemiology ; Cross-Sectional Studies ; Communicable Disease Control ; Socioeconomic Factors ; Anxiety/epidemiology ; Health Status ; Depression/epidemiology
Language	English
Publishing date	2023-05-04
Publishing country	Switzerland
Document type	Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph20095722
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