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Vitamin C Transporters, Recycling and the Bystander Effect in the Nervous System: SVCT2 versus Gluts.

Nualart F, Mack L, García A, Cisternas P, Bongarzone ER, Heitzer M, Jara N, Martínez F, Ferrada L, Espinoza F, Baeza V, Salazar K - J Stem Cell Res Ther (2014)

Bottom Line: After entry into cells within the central nervous system (CNS) through sodium vitamin C transporters (SVCTs) and facilitative glucose transporters (GLUTs), vitamin C functions as a neuromodulator, enzymatic cofactor, and reactive oxygen species (ROS) scavenger; it also stimulates differentiation.Additionally, we will describe SVCT and GLUT expression in different cells of the brain as well as SVCT2 distribution in tanycytes and astrocytes of the hypothalamic region.Finally, we will describe vitamin C recycling in the brain, which is mediated by a metabolic interaction between astrocytes and neurons, and the role of the "bystander effect" in the recycling mechanism of vitamin C in both normal and pathological conditions.

View Article: PubMed Central - PubMed

Affiliation: Center for Advanced Microscopy CMA BIO-BIO, Neurobiology and Stem cell Laboratory, Concepcion University, Chile.

ABSTRACT
Vitamin C is an essential micronutrient in the human diet; its deficiency leads to a number of symptoms and ultimately death. After entry into cells within the central nervous system (CNS) through sodium vitamin C transporters (SVCTs) and facilitative glucose transporters (GLUTs), vitamin C functions as a neuromodulator, enzymatic cofactor, and reactive oxygen species (ROS) scavenger; it also stimulates differentiation. In this review, we will compare the molecular and structural aspects of vitamin C and glucose transporters and their expression in endothelial or choroid plexus cells, which form part of the blood-brain barrier and blood-cerebrospinal fluid (CSF) barrier, respectively. Additionally, we will describe SVCT and GLUT expression in different cells of the brain as well as SVCT2 distribution in tanycytes and astrocytes of the hypothalamic region. Finally, we will describe vitamin C recycling in the brain, which is mediated by a metabolic interaction between astrocytes and neurons, and the role of the "bystander effect" in the recycling mechanism of vitamin C in both normal and pathological conditions.

No MeSH data available.


Related in: MedlinePlus

Comparative membrane topologies of Class I, II and III glucose transporters and the vitamin C transporter, SVCT2Class I, II and III glucose transporters as well as SVCT2 have 12 putative transmembrane domains (TM; numbers 1–12) base on prediction algorithms for transmembrane topology. A,B. The signature sequences conserved between classes I and II (A) and class III (B) glucose transporters are shown in boxes. Differences between the position of the large extracellular loop containing the N-glycosylation site, the proline-containing motif between TM6 and TM7, and the presence of a dileucine motif in the amino-terminal tail of class III glucose transporters (except for GLUT10) have been noted. C. The consensus sites for N-glycosylation and protein kinase C phosphorylation are shown. Important sequences for SVCT2 function and sorting include five histidine residues (H109, H203, H206, H269 and H413), the signature motif ((Q/E/P)NXGXXXXT(R/K/G)), a basolateral targeting sequence (LMAI) and a C-termini sequence for cell surface targeting, membrane incorporation, and retention (SYLPISPTFVGYTWKGLR) [105–107].
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Figure 1: Comparative membrane topologies of Class I, II and III glucose transporters and the vitamin C transporter, SVCT2Class I, II and III glucose transporters as well as SVCT2 have 12 putative transmembrane domains (TM; numbers 1–12) base on prediction algorithms for transmembrane topology. A,B. The signature sequences conserved between classes I and II (A) and class III (B) glucose transporters are shown in boxes. Differences between the position of the large extracellular loop containing the N-glycosylation site, the proline-containing motif between TM6 and TM7, and the presence of a dileucine motif in the amino-terminal tail of class III glucose transporters (except for GLUT10) have been noted. C. The consensus sites for N-glycosylation and protein kinase C phosphorylation are shown. Important sequences for SVCT2 function and sorting include five histidine residues (H109, H203, H206, H269 and H413), the signature motif ((Q/E/P)NXGXXXXT(R/K/G)), a basolateral targeting sequence (LMAI) and a C-termini sequence for cell surface targeting, membrane incorporation, and retention (SYLPISPTFVGYTWKGLR) [105–107].

Mentions: Vitamin C is a micronutrient essential for normal metabolic function; its deficiency in the human diet results in scurvy that is characterized by bleeding gums, impaired wound healing, petechiae, perifollicular hemorrhage, anemia, fatigue, depression, and ultimately death [1]. In the majority of mammals, vitamin C is synthesized in the liver; however, humans, other primates, and guinea pigs have lost their capacity to synthesize vitamin C due to the presence of a non-functional L-gulono-gamma-lactone oxidase gene, which is necessary for the last step in ascorbic acid (AA) biosynthesis [2]. In the blood, vitamin C levels reach up to 50 μM with most in its reduced form, AA, and only 5–10% in its oxidized form, dehydroascorbic acid (DHA). Independent of the capacity to synthesize vitamin C, efficient incorporation into the cells is crucial. AA is actively incorporated into the cytoplasmic membrane by sodium vitamin C transporters (SVCTs), and DHA uptake is mediated by facilitative glucose transporters (GLUTs) [3,4]. Specifically, GLUT1 and GLUT3 are mainly responsible for DHA uptake by cells of the central nervous system (CNS; Figure 1) [5,6].


Vitamin C Transporters, Recycling and the Bystander Effect in the Nervous System: SVCT2 versus Gluts.

Nualart F, Mack L, García A, Cisternas P, Bongarzone ER, Heitzer M, Jara N, Martínez F, Ferrada L, Espinoza F, Baeza V, Salazar K - J Stem Cell Res Ther (2014)

Comparative membrane topologies of Class I, II and III glucose transporters and the vitamin C transporter, SVCT2Class I, II and III glucose transporters as well as SVCT2 have 12 putative transmembrane domains (TM; numbers 1–12) base on prediction algorithms for transmembrane topology. A,B. The signature sequences conserved between classes I and II (A) and class III (B) glucose transporters are shown in boxes. Differences between the position of the large extracellular loop containing the N-glycosylation site, the proline-containing motif between TM6 and TM7, and the presence of a dileucine motif in the amino-terminal tail of class III glucose transporters (except for GLUT10) have been noted. C. The consensus sites for N-glycosylation and protein kinase C phosphorylation are shown. Important sequences for SVCT2 function and sorting include five histidine residues (H109, H203, H206, H269 and H413), the signature motif ((Q/E/P)NXGXXXXT(R/K/G)), a basolateral targeting sequence (LMAI) and a C-termini sequence for cell surface targeting, membrane incorporation, and retention (SYLPISPTFVGYTWKGLR) [105–107].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126260&req=5

Figure 1: Comparative membrane topologies of Class I, II and III glucose transporters and the vitamin C transporter, SVCT2Class I, II and III glucose transporters as well as SVCT2 have 12 putative transmembrane domains (TM; numbers 1–12) base on prediction algorithms for transmembrane topology. A,B. The signature sequences conserved between classes I and II (A) and class III (B) glucose transporters are shown in boxes. Differences between the position of the large extracellular loop containing the N-glycosylation site, the proline-containing motif between TM6 and TM7, and the presence of a dileucine motif in the amino-terminal tail of class III glucose transporters (except for GLUT10) have been noted. C. The consensus sites for N-glycosylation and protein kinase C phosphorylation are shown. Important sequences for SVCT2 function and sorting include five histidine residues (H109, H203, H206, H269 and H413), the signature motif ((Q/E/P)NXGXXXXT(R/K/G)), a basolateral targeting sequence (LMAI) and a C-termini sequence for cell surface targeting, membrane incorporation, and retention (SYLPISPTFVGYTWKGLR) [105–107].
Mentions: Vitamin C is a micronutrient essential for normal metabolic function; its deficiency in the human diet results in scurvy that is characterized by bleeding gums, impaired wound healing, petechiae, perifollicular hemorrhage, anemia, fatigue, depression, and ultimately death [1]. In the majority of mammals, vitamin C is synthesized in the liver; however, humans, other primates, and guinea pigs have lost their capacity to synthesize vitamin C due to the presence of a non-functional L-gulono-gamma-lactone oxidase gene, which is necessary for the last step in ascorbic acid (AA) biosynthesis [2]. In the blood, vitamin C levels reach up to 50 μM with most in its reduced form, AA, and only 5–10% in its oxidized form, dehydroascorbic acid (DHA). Independent of the capacity to synthesize vitamin C, efficient incorporation into the cells is crucial. AA is actively incorporated into the cytoplasmic membrane by sodium vitamin C transporters (SVCTs), and DHA uptake is mediated by facilitative glucose transporters (GLUTs) [3,4]. Specifically, GLUT1 and GLUT3 are mainly responsible for DHA uptake by cells of the central nervous system (CNS; Figure 1) [5,6].

Bottom Line: After entry into cells within the central nervous system (CNS) through sodium vitamin C transporters (SVCTs) and facilitative glucose transporters (GLUTs), vitamin C functions as a neuromodulator, enzymatic cofactor, and reactive oxygen species (ROS) scavenger; it also stimulates differentiation.Additionally, we will describe SVCT and GLUT expression in different cells of the brain as well as SVCT2 distribution in tanycytes and astrocytes of the hypothalamic region.Finally, we will describe vitamin C recycling in the brain, which is mediated by a metabolic interaction between astrocytes and neurons, and the role of the "bystander effect" in the recycling mechanism of vitamin C in both normal and pathological conditions.

View Article: PubMed Central - PubMed

Affiliation: Center for Advanced Microscopy CMA BIO-BIO, Neurobiology and Stem cell Laboratory, Concepcion University, Chile.

ABSTRACT
Vitamin C is an essential micronutrient in the human diet; its deficiency leads to a number of symptoms and ultimately death. After entry into cells within the central nervous system (CNS) through sodium vitamin C transporters (SVCTs) and facilitative glucose transporters (GLUTs), vitamin C functions as a neuromodulator, enzymatic cofactor, and reactive oxygen species (ROS) scavenger; it also stimulates differentiation. In this review, we will compare the molecular and structural aspects of vitamin C and glucose transporters and their expression in endothelial or choroid plexus cells, which form part of the blood-brain barrier and blood-cerebrospinal fluid (CSF) barrier, respectively. Additionally, we will describe SVCT and GLUT expression in different cells of the brain as well as SVCT2 distribution in tanycytes and astrocytes of the hypothalamic region. Finally, we will describe vitamin C recycling in the brain, which is mediated by a metabolic interaction between astrocytes and neurons, and the role of the "bystander effect" in the recycling mechanism of vitamin C in both normal and pathological conditions.

No MeSH data available.


Related in: MedlinePlus