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Article ; Online: Identification of Structural Determinants of the Transport of the Dehydroascorbic Acid Mediated by Glucose Transport GLUT1.

Villagrán, Marcelo / Burgos, Carlos F / Rivas, Coralia I / Mardones, Lorena

2023 Volume 28, Issue 2

Abstract: GLUT1 is a facilitative glucose transporter that can transport oxidized vitamin C (i.e., dehydroascorbic acid) and complements the action of reduced vitamin C transporters. To identify the residues involved in human GLUT1's transport of dehydroascorbic ... ...

Abstract	GLUT1 is a facilitative glucose transporter that can transport oxidized vitamin C (i.e., dehydroascorbic acid) and complements the action of reduced vitamin C transporters. To identify the residues involved in human GLUT1's transport of dehydroascorbic acid, we performed docking studies in the 5 Å grid of the glucose-binding cavity of GLUT1. The interactions of the bicyclic hemiacetal form of dehydroascorbic acid with GLUT1 through hydrogen bonds with the -OH group of C3 and C5 were less favorable than the interactions with the sugars transported by GLUT1. The eight most relevant residues in such interactions (i.e., F26, Q161, I164, Q282, Y292, and W412) were mutated to alanine to perform functional studies for dehydroascorbic acid and the glucose analog, 2-deoxiglucose, in
MeSH term(s)	Humans ; Ascorbic Acid ; Biological Transport ; Dehydroascorbic Acid/metabolism ; Glucose ; Glucose Transporter Type 1/chemistry ; Glucose Transporter Type 1/genetics
Chemical Substances	Ascorbic Acid (PQ6CK8PD0R) ; Dehydroascorbic Acid (Y2Z3ZTP9UM) ; Glucose (IY9XDZ35W2) ; Glucose Transporter Type 1 ; SLC2A1 protein, human
Language	English
Publishing date	2023-01-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules28020521
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Article ; Online: Transport of Vitamin C in Cancer.

Muñoz-Montesino, Carola / Peña, Eduardo / Roa, Francisco J / Sotomayor, Kirsty / Escobar, Elizabeth / Rivas, Coralia I

Antioxidants & redox signaling

2021 Volume 35, Issue 1, Page(s) 61–74

Abstract: Significance: ...

Abstract	Significance:
MeSH term(s)	Antioxidants/metabolism ; Ascorbic Acid/metabolism ; Dehydroascorbic Acid/metabolism ; Glucose Transport Proteins, Facilitative/metabolism ; Humans ; Mitochondria/metabolism ; Neoplasms/metabolism ; Sodium-Coupled Vitamin C Transporters/metabolism
Chemical Substances	Antioxidants ; Glucose Transport Proteins, Facilitative ; Sodium-Coupled Vitamin C Transporters ; Ascorbic Acid (PQ6CK8PD0R) ; Dehydroascorbic Acid (Y2Z3ZTP9UM)
Language	English
Publishing date	2021-04-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1483836-9
ISSN	1557-7716 ; 1523-0864
ISSN (online)	1557-7716
ISSN	1523-0864
DOI	10.1089/ars.2020.8166
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Article: Co-Formulation of Recombinant Porcine IL-18 Enhances the Onset of Immune Response in a New

Hidalgo-Gajardo, Angela / Gutiérrez, Nicolás / Lamazares, Emilio / Espinoza, Felipe / Escobar-Riquelme, Fernanda / Leiva, María J / Villavicencio, Carla / Mena-Ulecia, Karel / Montesino, Raquel / Altamirano, Claudia / Sánchez, Oliberto / Rivas, Coralia I / Ruíz, Álvaro / Toledo, Jorge R

Vaccines

2023 Volume 11, Issue 12

Abstract: Pig is one of the most consumed meats worldwide. One of the main conditions for pig production is Porcine Enteropathy caused ... ...

Abstract	Pig is one of the most consumed meats worldwide. One of the main conditions for pig production is Porcine Enteropathy caused by
Language	English
Publishing date	2023-11-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines11121788
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Article: PrP

Panes, Jessica D / Saavedra, Paulina / Pineda, Benjamin / Escobar, Kathleen / Cuevas, Magdalena E / Moraga-Cid, Gustavo / Fuentealba, Jorge / Rivas, Coralia I / Rezaei, Human / Muñoz-Montesino, Carola

Frontiers in molecular neuroscience

2021 Volume 14, Page(s) 762918

Abstract: After the discovery of prion phenomenon, the physiological role of the cellular prion protein ( ... ...

Abstract	After the discovery of prion phenomenon, the physiological role of the cellular prion protein (PrP
Language	English
Publishing date	2021-11-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2452967-9
ISSN	1662-5099
ISSN	1662-5099
DOI	10.3389/fnmol.2021.762918
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Article: Therapeutic Use of Vitamin C in Cancer: Physiological Considerations.

Roa, Francisco J / Peña, Eduardo / Gatica, Marcell / Escobar-Acuña, Kathleen / Saavedra, Paulina / Maldonado, Mafalda / Cuevas, Magdalena E / Moraga-Cid, Gustavo / Rivas, Coralia I / Muñoz-Montesino, Carola

Frontiers in pharmacology

2020 Volume 11, Page(s) 211

Abstract: Since the early studies of William J. McCormick in the 1950s, vitamin C has been proposed as a candidate for the treatment of cancer. A number of reports have shown that pharmacological concentrations of vitamin C selectively kill cancer ... ...

Abstract	Since the early studies of William J. McCormick in the 1950s, vitamin C has been proposed as a candidate for the treatment of cancer. A number of reports have shown that pharmacological concentrations of vitamin C selectively kill cancer cells
Language	English
Publishing date	2020-03-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2020.00211
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Article ; Online: GLUT1 and GLUT8 support lactose synthesis in Golgi of murine mammary epithelial cells.

Villagrán, Marcelo / Muñoz, Mirna / Inostroza, Eveling / Venegas, Camila / Ruminot, Iván / Parra-Valencia, Esteban / Maldonado, Mafalda / Del Pozo, Reginald / Rivas, Coralia I / Vera, Juan Carlos / Mardones, Lorena

Journal of physiology and biochemistry

2019 Volume 75, Issue 2, Page(s) 209–215

Abstract: The mammary gland increases energy requirements during pregnancy and lactation to support epithelial proliferation and milk nutrients synthesis. Lactose, the principal carbohydrate of the milk, is synthetized in the Golgi of mammary epithelial cells by ... ...

Abstract	The mammary gland increases energy requirements during pregnancy and lactation to support epithelial proliferation and milk nutrients synthesis. Lactose, the principal carbohydrate of the milk, is synthetized in the Golgi of mammary epithelial cells by lactose synthase from glucose and UPD galactose. We studied the temporal changes in the expression of GLUT1 and GLUT8 in mammary gland and their association with lactose synthesis and proliferation in BALB/c mice. Six groups were used: virgin, pregnant at 2 and 17 days, lactating at 2 and 10 days, and weaning at 2 days. Temporal expression of GLUT1 and GLUT8 transporters by qPCR, western blot and immunohistochemistry, and its association with lactalbumin, Ki67, and cytokeratin 18 within mammary tissue was studied, along with subcellular localization. GLUT1 and GLUT8 transporters increased their expression during mammary gland progression, reaching 20-fold increasing in GLUT1 mRNA at lactation (p < 0.05) and 2-fold at protein level for GLUT1 and GLUT8 (p < 0.05 and 0.01, respectively). The temporal expression pattern was shared with cytokeratin 18 and Ki67 (p < 0.01). Endogenous GLUT8 partially co-localized with 58 K protein and α-lactalbumin in mammary tissue and with Golgi membrane-associated protein 130 in isolated epithelial cells. The spatial-temporal synchrony between expression of GLUT8/GLUT1 and alveolar cell proliferation, and its localization in cis-Golgi associated to lactose synthase complex, suggest that both transporters are involved in glucose uptake into this organelle, supporting lactose synthesis.
MeSH term(s)	Animals ; Epithelial Cells/immunology ; Epithelial Cells/metabolism ; Female ; Glucose/metabolism ; Glucose Transport Proteins, Facilitative/genetics ; Glucose Transport Proteins, Facilitative/metabolism ; Glucose Transporter Type 1/genetics ; Glucose Transporter Type 1/metabolism ; Golgi Apparatus/metabolism ; Keratin-18/metabolism ; Lactalbumin/metabolism ; Lactation ; Lactose/biosynthesis ; Lactose Synthase/metabolism ; Mammary Glands, Animal/metabolism ; Mice ; Mice, Inbred BALB C ; Peptides/metabolism ; Pregnancy ; RNA, Messenger/metabolism ; Retinoblastoma-Like Protein p130/metabolism ; Time Factors ; Weaning
Chemical Substances	Glucose Transport Proteins, Facilitative ; Glucose Transporter Type 1 ; KIA7 protein ; Keratin-18 ; Peptides ; RNA, Messenger ; Rbl2 protein, mouse ; Retinoblastoma-Like Protein p130 ; Slc2a1 protein, mouse ; Slc2a8 protein, mouse ; Lactalbumin (9013-90-5) ; Lactose Synthase (EC 2.4.1.22) ; Glucose (IY9XDZ35W2) ; Lactose (J2B2A4N98G)
Language	English
Publishing date	2019-04-24
Publishing country	Spain
Document type	Journal Article
ZDB-ID	1325104-1
ISSN	1877-8755 ; 0034-9402 ; 1138-7548
ISSN (online)	1877-8755
ISSN	0034-9402 ; 1138-7548
DOI	10.1007/s13105-019-00679-3
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Zs.B 198: Show issues

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Article ; Online: Expression and purification of the surface proteins from Andes virus.

Beltrán-Ortiz, Camila E / Starck-Mendez, Maria F / Fernández, Yaiza / Farnós, Omar / González, Eddy E / Rivas, Coralia I / Camacho, F / Zuñiga, Felipe A / Toledo, Jorge R / Sánchez, Oliberto

Protein expression and purification

2017 Volume 139, Page(s) 63–70

Abstract: Andes virus is the main causative agent of Hantavirus cardiopulmonary syndrome in South America. There are currently no vaccines or treatments against Andes virus. However, there are several evidences suggesting that antibodies against Andes virus ... ...

Abstract	Andes virus is the main causative agent of Hantavirus cardiopulmonary syndrome in South America. There are currently no vaccines or treatments against Andes virus. However, there are several evidences suggesting that antibodies against Andes virus envelope glycoproteins may be enough to confer full protection against Hantavirus cardiopulmonary syndrome. The goal of the present work was to express, purify and characterize the extracellular domains of Andes virus glycoproteins Gn and Gc. We generated two adenoviral vectors encoding the extracellular domains of Andes virus glycoproteins Gn and Gc. Both molecules were expressed by adenoviral transduction in SiHa cells. We found that sGc ectodomain was mainly secreted into the culture medium, whereas sGn was predominantly retained inside the cells. Both molecules were expressed at very low concentrations (below 1 μg/mL). Treatment with the proteasome inhibitor ALLN raised sGc concentration in the cell culture medium, but did not affect expression levels of sGn. Both ectodomains were purified by immobilized metal ion affinity chromatography, and were recognized by sera from persons previously exposed to Andes virus. To our knowledge, this is the first work that addresses the expression and purification of Andes virus glycoproteins Gn and Gc. Our results demonstrate that sGn and sGc maintain epitopes that are exposed on the surface of the viral envelope. However, our work also highlights the need to explore new strategies to achieve high-level expression of these proteins for development of a vaccine candidate against Andes virus.
MeSH term(s)	Cell Line, Tumor ; Electrophoresis, Polyacrylamide Gel ; Hantavirus/genetics ; Humans ; Recombinant Proteins/chemistry ; Recombinant Proteins/genetics ; Recombinant Proteins/isolation & purification ; Recombinant Proteins/metabolism ; Viral Envelope Proteins/chemistry ; Viral Envelope Proteins/genetics ; Viral Envelope Proteins/isolation & purification ; Viral Envelope Proteins/metabolism
Chemical Substances	Recombinant Proteins ; Viral Envelope Proteins
Language	English
Publishing date	2017-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	1055455-5
ISSN	1096-0279 ; 1046-5928
ISSN (online)	1096-0279
ISSN	1046-5928
DOI	10.1016/j.pep.2015.09.013
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Article: Data on SVCT2 transporter expression and localization in cancer cell lines and tissues

Roa, Francisco J. / Peña, Eduardo / Inostroza, Eveling / Sotomayor, Kirsty / González, Mauricio / Gutierrez-Castro, Francisco A. / Maurin, Michelle / Sweet, Karen / Labrousse, Claire / Gatica, Marcell / Aylwin, Carlos F. / Mendoza, Pamela / Maldonado, Mafalda / Delgado, Carolina / Madariaga, Jaime / Panes, Jessica / Silva-Grecchi, Tiare / Concha, Ilona I. / Moraga-Cid, Gustavo /

Reyes, Alejandro M. / Muñoz-Montesino, Carola / Vera, Juan Carlos / Rivas, Coralia I.

Data in Brief. 2019 Aug., v. 25

2019

Abstract: The data presented in this article are related to the research paper entitled “Increased expression of mitochondrial sodium-coupled ascorbic acid transporter-2 (mitSVCT2) as a central feature in breast cancer”, available in Free Radical Biology and ... ...

Abstract	The data presented in this article are related to the research paper entitled “Increased expression of mitochondrial sodium-coupled ascorbic acid transporter-2 (mitSVCT2) as a central feature in breast cancer”, available in Free Radical Biology and Medicine Journal [1]. In this article, we examined the SVCT2 transporter expression in various breast cancer cell lines using RT-PCR and Western blot assays. In addition, we analyzed the subcellular localization of SVCT2 by immunofluorescence colocalization assays and cellular fractionation experiments. Finally, an analysis of different cancer tissue microarrays immunostained for SVCT2 and imaged by The Human Protein Atlas (https://www.proteinatlas.org) is presented.
Keywords	Western blotting ; ascorbic acid ; breast neoplasms ; fluorescent antibody technique ; fractionation ; mitochondria ; neoplasm cells
Language	English
Dates of publication	2019-08
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	2786545-9
ISSN	2352-3409
ISSN	2352-3409
DOI	10.1016/j.dib.2019.103972
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Data on SVCT2 transporter expression and localization in cancer cell lines and tissues.

Roa, Francisco J / Peña, Eduardo / Inostroza, Eveling / Sotomayor, Kirsty / González, Mauricio / Gutierrez-Castro, Francisco A / Maurin, Michelle / Sweet, Karen / Labrousse, Claire / Gatica, Marcell / Aylwin, Carlos F / Mendoza, Pamela / Maldonado, Mafalda / Delgado, Carolina / Madariaga, Jaime / Panes, Jessica / Silva-Grecchi, Tiare / Concha, Ilona I / Moraga-Cid, Gustavo /

Reyes, Alejandro M / Muñoz-Montesino, Carola / Vera, Juan Carlos / Rivas, Coralia I

Data in brief

2019 Volume 25, Page(s) 103972

Abstract: The data presented in this article are related to the research paper entitled "Increased expression of mitochondrial sodium-coupled ascorbic acid transporter-2 (mitSVCT2) as a central feature in breast cancer", available in Free Radical Biology and ... ...

Abstract	The data presented in this article are related to the research paper entitled "Increased expression of mitochondrial sodium-coupled ascorbic acid transporter-2 (mitSVCT2) as a central feature in breast cancer", available in Free Radical Biology and Medicine Journal [1]. In this article, we examined the SVCT2 transporter expression in various breast cancer cell lines using RT-PCR and Western blot assays. In addition, we analyzed the subcellular localization of SVCT2 by immunofluorescence colocalization assays and cellular fractionation experiments. Finally, an analysis of different cancer tissue microarrays immunostained for SVCT2 and imaged by The Human Protein Atlas (https://www.proteinatlas.org) is presented.
Language	English
Publishing date	2019-05-06
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2786545-9
ISSN	2352-3409 ; 2352-3409
ISSN (online)	2352-3409
ISSN	2352-3409
DOI	10.1016/j.dib.2019.103972
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Article ; Online: Increased expression of mitochondrial sodium-coupled ascorbic acid transporter-2 (mitSVCT2) as a central feature in breast cancer.

Peña, Eduardo / Roa, Francisco J / Inostroza, Eveling / Sotomayor, Kirsty / González, Mauricio / Gutierrez-Castro, Francisco A / Maurin, Michelle / Sweet, Karen / Labrousse, Claire / Gatica, Marcell / Aylwin, Carlos F / Mendoza, Pamela / Maldonado, Mafalda / Delgado, Carolina / Madariaga, Jaime / Panes, Jessica / Silva-Grecchi, Tiare / Concha, Ilona I / Moraga-Cid, Gustavo /

Reyes, Alejandro M / Muñoz-Montesino, Carola / Vera, Juan Carlos / Rivas, Coralia I

Free radical biology & medicine

2019 Volume 135, Page(s) 283–292

Abstract: The potential role of vitamin C in cancer prevention and treatment remains controversial. While normal human cells obtain vitamin C as ascorbic acid, the prevalent form of vitamin C in vivo, the uptake mechanisms by which cancer cells acquire vitamin C ... ...

Abstract	The potential role of vitamin C in cancer prevention and treatment remains controversial. While normal human cells obtain vitamin C as ascorbic acid, the prevalent form of vitamin C in vivo, the uptake mechanisms by which cancer cells acquire vitamin C has remained unclear. The aim of this study is to characterize how breast cancer cells acquire vitamin C. For this, we determined the expression of vitamin C transporters in normal and breast cancer tissue samples, and in ZR-75, MCF-7, MDA-231 and MDA-468 breast cancer cell lines. At the same time, reduced (AA) and oxidized (DHA) forms of vitamin C uptake experiments were performed in all cell lines. We show here that human breast cancer tissues differentially express a form of SVCT2 transporter, that is systematically absent in normal breast tissues and it is increased in breast tumors. In fact, estrogen receptor negative breast cancer tissue, exhibit the most elevated SVCT2 expression levels. Despite this, our analysis in breast cancer cell lines showed that these cells are not able to uptake ascorbic acid and depend on glucose transporter for the acquisition of vitamin C by a bystander effect. This is consistent with our observations that this form of SVCT2 is completely absent from the plasma membrane and is overexpressed in mitochondria of breast cancer cells, where it mediates ascorbic acid transport. This work shows that breast cancer cells acquire vitamin C in its oxidized form and are capable of accumulated high concentrations of the reduced form. Augmented expression of an SVCT2 mitochondrial form appears to be a common hallmark across all human cancers and might have implications in cancer cells survival capacity against pro-oxidant environments.
MeSH term(s)	Ascorbic Acid/metabolism ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Bystander Effect ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; MCF-7 Cells ; Mitochondria/genetics ; Mitochondria/pathology ; Mitochondrial Membrane Transport Proteins/genetics ; Oxidation-Reduction ; Reactive Oxygen Species/metabolism ; Sodium/metabolism ; Sodium-Coupled Vitamin C Transporters/genetics
Chemical Substances	Mitochondrial Membrane Transport Proteins ; Reactive Oxygen Species ; SLC23A2 protein, human ; Sodium-Coupled Vitamin C Transporters ; Sodium (9NEZ333N27) ; Ascorbic Acid (PQ6CK8PD0R)
Language	English
Publishing date	2019-03-19
Publishing country	United States
Document type	Journal Article ; 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.2019.03.015
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