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Article: Nox1-based NADPH oxidase regulates the Par protein complex activity to control cell polarization.

Valdivia, Alejandra / Duran, Charity / Lee, Mingyoung / Williams, Holly C / Lee, Moo-Yeol / San Martin, Alejandra

Frontiers in cell and developmental biology

2023 Volume 11, Page(s) 1231489

Abstract: Cell migration is essential for many biological and pathological processes. Establishing cell polarity with a trailing edge and forming a single lamellipodium at the leading edge of the cell is crucial for efficient directional cell migration and is a ... ...

Abstract	Cell migration is essential for many biological and pathological processes. Establishing cell polarity with a trailing edge and forming a single lamellipodium at the leading edge of the cell is crucial for efficient directional cell migration and is a hallmark of mesenchymal cell motility. Lamellipodia formation is regulated by spatial-temporal activation of the small GTPases Rac and Cdc42 at the front edge, and RhoA at the rear end. At a molecular level, partitioning-defective (Par) protein complex comprising Par3, Par6, and atypical Protein Kinase (aPKC isoforms ζ and λ/ι) regulates front-rear axis polarization. At the front edge, integrin clustering activates Cdc42, prompting the formation of Par3/Par6/aPKC complexes to modulate MTOC positioning and microtubule stabilization. Consequently, the Par3/Par6/aPKC complex recruits Rac1-GEF Tiam to activate Rac1, leading to lamellipodium formation. At the rear end, RhoA-ROCK phosphorylates Par3 disrupting its interaction with Tiam and inactivating Rac1. RhoA activity at the rear end allows the formation of focal adhesions and stress fibers necessary to generate the traction forces that allow cell movement. Nox1-based NADPH oxidase is necessary for PDGF-induced migration
Language	English
Publishing date	2023-08-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2023.1231489
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Histopathological modeling of status epilepticus-induced brain damage based on

San Martín Molina, Isabel / Salo, Raimo A / Gröhn, Olli / Tohka, Jussi / Sierra, Alejandra

Frontiers in neuroscience

2022 Volume 16, Page(s) 944432

Abstract: Non-invasive magnetic resonance imaging (MRI) methods have proved useful in the diagnosis and prognosis of neurodegenerative diseases. However, the interpretation of imaging outcomes in terms of tissue pathology is still challenging. This study goes ... ...

Abstract	Non-invasive magnetic resonance imaging (MRI) methods have proved useful in the diagnosis and prognosis of neurodegenerative diseases. However, the interpretation of imaging outcomes in terms of tissue pathology is still challenging. This study goes beyond the current interpretation of
Language	English
Publishing date	2022-07-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2022.944432
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Article ; Online: Metabolic adaptation in hypoxia and cancer.

Paredes, Felipe / Williams, Holly C / San Martin, Alejandra

Cancer letters

2021 Volume 502, Page(s) 133–142

Abstract: The ability of tumor cells to adapt to changes in oxygen tension is essential for tumor development. Low oxygen concentration influences cellular metabolism and, thus, affects proliferation, migration, and invasion. A focal point of the cell's adaptation ...

Abstract	The ability of tumor cells to adapt to changes in oxygen tension is essential for tumor development. Low oxygen concentration influences cellular metabolism and, thus, affects proliferation, migration, and invasion. A focal point of the cell's adaptation to hypoxia is the transcription factor HIF1α (hypoxia-inducible factor 1 alpha), which affects the expression of specific gene networks involved in cellular energetics and metabolism. This review illustrates the mechanisms by which HIF1α-induced metabolic adaptation promotes angiogenesis, participates in the escape from immune recognition, and increases cancer cell antioxidant capacity. In addition to hypoxia, metabolic inhibition of 2-oxoglutarate-dependent dioxygenases regulates HIF1α stability and transcriptional activity. This phenomenon, known as pseudohypoxia, is frequently used by cancer cells to promote glycolytic metabolism to support biomass synthesis for cell growth and proliferation. In this review, we highlight the role of the most important metabolic intermediaries that are at the center of cancer's biology, and in particular, the participation of these metabolites in HIF1α retrograde signaling during the establishment of pseudohypoxia. Finally, we will discuss how these changes affect both the development of cancers and their resistance to treatment.
MeSH term(s)	Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/chemistry ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Neoplasms/genetics ; Neoplasms/metabolism ; Protein Stability ; Signal Transduction ; Tumor Hypoxia
Chemical Substances	HIF1A protein, human ; Hypoxia-Inducible Factor 1, alpha Subunit
Language	English
Publishing date	2021-01-11
Publishing country	Ireland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2020.12.020
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Article ; Online: Malestar emocional en pacientes de cuidados paliativos: desafíos y oportunidades.

Bernales, Margarita / Chandía, Alejandra / San Martín, María Jesús

Revista medica de Chile

2019 Volume 147, Issue 6, Page(s) 813–814

Title translation	Emotional malaise in palliative care patients: challenges and opportunities.
MeSH term(s)	Chile ; Humans ; Neoplasms/psychology ; Neoplasms/therapy ; Palliative Care/methods ; Palliative Care/psychology ; Psychological Distress
Language	Spanish
Publishing date	2019-12-20
Publishing country	Chile
Document type	Letter
ZDB-ID	732136-3
ISSN	0717-6163 ; 0034-9887
ISSN (online)	0717-6163
ISSN	0034-9887
DOI	10.4067/S0034-98872019000600813
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Article: Poldip2 takes a central role in metabolic reprograming.

Paredes, Felipe / Suster, Izabela / Martin, Alejandra San

Oncoscience

2018 Volume 5, Issue 5-6, Page(s) 130–131

Language	English
Publishing date	2018-06-23
Publishing country	United States
Document type	Editorial
ISSN	2331-4737
ISSN	2331-4737
DOI	10.18632/oncoscience.419
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Article ; Online: The Role of Fatty Acid Synthase in the Vascular Smooth Muscle Cell to Foam Cell Transition.

Bogan, Bethany J / Williams, Holly C / Holden, Claire M / Patel, Vraj / Joseph, Giji / Fierro, Christopher / Sepulveda, Hugo / Taylor, W Robert / Rezvan, Amir / San Martin, Alejandra

Cells

2024 Volume 13, Issue 8

Abstract: Vascular smooth muscle cells (VSMCs), in their contractile and differentiated state, are fundamental for maintaining vascular function. Upon exposure to cholesterol (CHO), VSMCs undergo dedifferentiation, adopting characteristics of foam cells-lipid- ... ...

Abstract	Vascular smooth muscle cells (VSMCs), in their contractile and differentiated state, are fundamental for maintaining vascular function. Upon exposure to cholesterol (CHO), VSMCs undergo dedifferentiation, adopting characteristics of foam cells-lipid-laden, macrophage-like cells pivotal in atherosclerotic plaque formation. CHO uptake by VSMCs leads to two primary pathways: ABCA1-mediated efflux or storage in lipid droplets as cholesterol esters (CEs). CE formation, involving the condensation of free CHO and fatty acids, is catalyzed by sterol O-acyltransferase 1 (SOAT1). The necessary fatty acids are synthesized by the lipogenic enzyme fatty acid synthase (FASN), which we found to be upregulated in atherosclerotic human coronary arteries. This observation led us to hypothesize that FASN-mediated fatty acid biosynthesis is crucial in the transformation of VSMCs into foam cells. Our study reveals that CHO treatment upregulates FASN in human aortic SMCs, concurrent with increased expression of CD68 and upregulation of KLF4, markers associated with the foam cell transition. Crucially, downregulation of FASN inhibits the CHO-induced upregulation of CD68 and KLF4 in VSMCs. Additionally, FASN-deficient VSMCs exhibit hindered lipid accumulation and an impaired transition to the foam cell phenotype following CHO exposure, while the addition of the fatty acid palmitate, the main FASN product, exacerbates this transition. FASN-deficient cells also show decreased SOAT1 expression and elevated ABCA1. Notably, similar effects are observed in KLF4-deficient cells. Our findings demonstrate that FASN plays an essential role in the CHO-induced upregulation of KLF4 and the VSMC to foam cell transition and suggest that targeting FASN could be a novel therapeutic strategy to regulate VSMC phenotypic modulation.
MeSH term(s)	Animals ; Humans ; Atherosclerosis/pathology ; Atherosclerosis/metabolism ; Cholesterol/metabolism ; Fatty Acid Synthases/metabolism ; Fatty Acid Synthases/genetics ; Fatty Acids/metabolism ; Foam Cells/metabolism ; Kruppel-Like Factor 4 ; Muscle, Smooth, Vascular/metabolism ; Muscle, Smooth, Vascular/cytology ; Myocytes, Smooth Muscle/metabolism
Chemical Substances	Cholesterol (97C5T2UQ7J) ; Fatty Acid Synthases (EC 2.3.1.85) ; Fatty Acids ; KLF4 protein, human ; Kruppel-Like Factor 4 ; FASN protein, human (EC 2.3.1.85)
Language	English
Publishing date	2024-04-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells13080658
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Article ; Online: HERPUD1 governs tumor cell mitochondrial function via inositol 1,4,5-trisphosphate receptor-mediated calcium signaling.

Paredes, Felipe / Navarro-Marquez, Mario / Quiroga, Clara / Jiménez-Gallegos, Danica / Yeligar, Samantha M / Parra, Valentina / Müller, Marioly / Chiong, Mario / Quest, Andrew F G / San Martin, Alejandra / Lavandero, Sergio

Free radical biology & medicine

2023 Volume 211, Page(s) 24–34

Abstract: The intricate relationship between calcium ( ... ...

Abstract	The intricate relationship between calcium (Ca
MeSH term(s)	Humans ; Calcium/metabolism ; Calcium Signaling/physiology ; Inositol 1,4,5-Trisphosphate Receptors/genetics ; Inositol 1,4,5-Trisphosphate Receptors/metabolism ; Inositol/metabolism ; Mitochondria/genetics ; Mitochondria/metabolism ; Neoplasms/genetics ; Neoplasms/metabolism ; Transcription Factors/metabolism
Chemical Substances	Calcium (SY7Q814VUP) ; Inositol 1,4,5-Trisphosphate Receptors ; Inositol (4L6452S749) ; 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester (139890-68-9) ; Transcription Factors
Language	English
Publishing date	2023-12-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	807032-5
ISSN	1873-4596 ; 0891-5849
ISSN (online)	1873-4596
ISSN	0891-5849
DOI	10.1016/j.freeradbiomed.2023.11.022
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Zs.A 2109: Show issues

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Article: Microstructural Tissue Changes in a Rat Model of Mild Traumatic Brain Injury.

Chary, Karthik / Narvaez, Omar / Salo, Raimo A / San Martín Molina, Isabel / Tohka, Jussi / Aggarwal, Manisha / Gröhn, Olli / Sierra, Alejandra

Frontiers in neuroscience

2021 Volume 15, Page(s) 746214

Abstract: Our study investigates the potential of diffusion MRI (dMRI), including diffusion tensor imaging (DTI), fixel-based analysis (FBA) and neurite orientation dispersion and density imaging (NODDI), to detect microstructural tissue abnormalities in rats ... ...

Abstract	Our study investigates the potential of diffusion MRI (dMRI), including diffusion tensor imaging (DTI), fixel-based analysis (FBA) and neurite orientation dispersion and density imaging (NODDI), to detect microstructural tissue abnormalities in rats after mild traumatic brain injury (mTBI). The brains of sham-operated and mTBI rats 35 days after lateral fluid percussion injury were imaged
Language	English
Publishing date	2021-11-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2021.746214
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Article ; Online: Metabolic regulation of the proteasome under hypoxia by Poldip2 controls fibrotic signaling in vascular smooth muscle cells.

Paredes, Felipe / Williams, Holly C / Suster, Izabela / Tejos, Macarena / Fuentealba, Roberto / Bogan, Bethany / Holden, Claire M / San Martin, Alejandra

Free radical biology & medicine

2022 Volume 195, Page(s) 283–297

Abstract: The polymerase delta interacting protein 2 (Poldip2) is a nuclear-encoded mitochondrial protein required for oxidative metabolism. Under hypoxia, Poldip2 expression is repressed by an unknown mechanism. Therefore, low levels of Poldip2 are required to ... ...

Abstract	The polymerase delta interacting protein 2 (Poldip2) is a nuclear-encoded mitochondrial protein required for oxidative metabolism. Under hypoxia, Poldip2 expression is repressed by an unknown mechanism. Therefore, low levels of Poldip2 are required to maintain glycolytic metabolism. The Cellular Communication Network Factor 2 (CCN2, Connective tissue growth factor, CTGF) is a profibrogenic molecule highly expressed in cancer and vascular inflammation in advanced atherosclerosis. Because CCN2 is upregulated under hypoxia and is associated with glycolytic metabolism, we hypothesize that Poldip2 downregulation is responsible for the upregulation of profibrotic signaling under hypoxia. Here, we report that Poldip2 is repressed under hypoxia by a mechanism that requires the activation of the enhancer of zeste homolog 2 repressive complex (EZH2) downstream from the Cyclin-Dependent Kinase 2 (CDK2). Importantly, we found that Poldip2 repression is required for CCN2 expression downstream of metabolic inhibition of the ubiquitin-proteasome system (UPS)-dependent stabilization of the serum response factor. Pharmacological or gene expression inhibition of CDK2 under hypoxia reverses Poldip2 downregulation, the inhibition of the UPS, and the expression of CCN2, collagen, and fibronectin. Thus, our findings connect cell cycle regulation and proteasome activity to mitochondrial function and fibrotic responses under hypoxia.
MeSH term(s)	Humans ; Proteasome Endopeptidase Complex/genetics ; Proteasome Endopeptidase Complex/metabolism ; Nuclear Proteins/metabolism ; Muscle, Smooth, Vascular/metabolism ; Signal Transduction ; Hypoxia/genetics ; Hypoxia/metabolism ; Connective Tissue Growth Factor/genetics ; Connective Tissue Growth Factor/metabolism
Chemical Substances	Proteasome Endopeptidase Complex (EC 3.4.25.1) ; Nuclear Proteins ; Connective Tissue Growth Factor (139568-91-5) ; POLDIP2 protein, human
Language	English
Publishing date	2022-12-31
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	807032-5
ISSN	1873-4596 ; 0891-5849
ISSN (online)	1873-4596
ISSN	0891-5849
DOI	10.1016/j.freeradbiomed.2022.12.098
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Article ; Online: Total error in lymphocyte subpopulations by flow cytometry-based in state of the art using Spanish EQAS data.

Comins-Boo, Alejandra / Pérez-Pla, Fernando / Irure-Ventura, Juan / López-Hoyos, Marcos / Blanco-Peris, Lydia / Martín Alonso, María Del Carmen / San Segundo Arribas, David

Clinical chemistry and laboratory medicine

2023 Volume 62, Issue 2, Page(s) 312–321

Abstract: Objectives: Flow cytometry analyses of lymphocyte subpopulations (T, B, NK) are crucial for enhancing clinical algorithms and research workflows. Estimating the total error (TE) values for the percentage and absolute number of lymphocyte subpopulations ... ...

Abstract	Objectives: Flow cytometry analyses of lymphocyte subpopulations (T, B, NK) are crucial for enhancing clinical algorithms and research workflows. Estimating the total error (TE) values for the percentage and absolute number of lymphocyte subpopulations using the state-of-the-art (SOTA) approach with real data from an external proficiency testing (EPT) scheme was performed. A comparison with previously published Biological Variability (BV)-based specifications was carried out. Methods: A total of 44,998 results from 86 laboratories over 10 years were analysed and divided into two five-year periods (2012-2016) and (2017-2021). Data come from the IC-1 Lymphocytes scheme of the Spanish External Quality Assurance System (EQAS) GECLID Program. This quantitative scheme includes percentages and absolute numbers of CD3 Results: A significant reduction in the SOTA-based TE for all lymphocyte subpopulations in 2017-2021 was observed compared to 2012-2016. The SOTA-based TE fulfils the minimum BV-based TE for percentages of lymphocyte subpopulations. The parameter with the best analytical performance calculated with SOTA (2017-2021 period)-based TE was the percentage of CD3 Conclusions: The values of SOTA-based specifications from external quality assurance program data are consistent and can be used to develop technical specifications. The technological improvement, quality commitment, standardization, and training, reduce TE. An update of TE every five years is therefore recommended. TE assessment in lymphocyte subsets is a helpful and reliable tool to improve laboratory performance and data-based decision-making trust.
MeSH term(s)	Humans ; Flow Cytometry ; Lymphocyte Subsets ; Killer Cells, Natural ; Lymphocyte Count ; Laboratory Proficiency Testing
Language	English
Publishing date	2023-08-07
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1418007-8
ISSN	1437-4331 ; 1434-6621 ; 1437-8523
ISSN (online)	1437-4331
ISSN	1434-6621 ; 1437-8523
DOI	10.1515/cclm-2023-0470
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