Tags

Type your tag names separated by a space and hit enter

Nitric oxide induces the expression of the monocarboxylate transporter MCT4 in cultured astrocytes by a cGMP-independent transcriptional activation.
Glia 2011; 59(12):1987-95GLIA

Abstract

The monocarboxylate transporter MCT4 is a proton-linked carrier particularly important for lactate release from highly glycolytic cells. In the central nervous system, MCT4 is exclusively expressed by astrocytes. Surprisingly, MCT4 expression in primary cultures of mouse cortical astrocytes is conspicuously low, suggesting that an external, nonastrocytic signal is necessary to obtain the observed pattern of expression in vivo. Here, we demonstrate that nitric oxide (NO), delivered by various NO donors, time- and dose-dependently induces MCT4 expression in cultured cortical astrocytes both at the mRNA and protein levels. In contrast, NO does not enhance the expression of MCT1, the other astrocytic monocarboxylate transporter. The transcriptional effect of NO is not mediated by a cGMP-dependent mechanism as shown by the absence of effect of a cGMP analog or of a selective guanylate cyclase inhibitor. NO causes an increase in astrocytic lactate transport capacity which requires the enhancement of MCT4 expression as both are prevented by the use of a specific siRNA against MCT4. In addition, cumulated lactate release by astrocytes over a period of 24 h was also enhanced by NO treatment. Our data suggest that NO represents a putative intercellular signal to control MCT4 expression in astrocytes and in doing so, to facilitate lactate transfer to other surrounding cell types in the central nervous system. © 2011 Wiley-Liss, Inc.

Authors+Show Affiliations

Département de Physiologie, Université de Lausanne, CH-1005 Lausanne, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21901758

Citation

Marcillac, Fabrice, et al. "Nitric Oxide Induces the Expression of the Monocarboxylate Transporter MCT4 in Cultured Astrocytes By a cGMP-independent Transcriptional Activation." Glia, vol. 59, no. 12, 2011, pp. 1987-95.
Marcillac F, Brix B, Repond C, et al. Nitric oxide induces the expression of the monocarboxylate transporter MCT4 in cultured astrocytes by a cGMP-independent transcriptional activation. Glia. 2011;59(12):1987-95.
Marcillac, F., Brix, B., Repond, C., Jöhren, O., & Pellerin, L. (2011). Nitric oxide induces the expression of the monocarboxylate transporter MCT4 in cultured astrocytes by a cGMP-independent transcriptional activation. Glia, 59(12), pp. 1987-95. doi:10.1002/glia.21240.
Marcillac F, et al. Nitric Oxide Induces the Expression of the Monocarboxylate Transporter MCT4 in Cultured Astrocytes By a cGMP-independent Transcriptional Activation. Glia. 2011;59(12):1987-95. PubMed PMID: 21901758.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nitric oxide induces the expression of the monocarboxylate transporter MCT4 in cultured astrocytes by a cGMP-independent transcriptional activation. AU - Marcillac,Fabrice, AU - Brix,Britta, AU - Repond,Cendrine, AU - Jöhren,Olaf, AU - Pellerin,Luc, Y1 - 2011/09/07/ PY - 2011/04/12/received PY - 2011/08/03/accepted PY - 2011/9/9/entrez PY - 2011/9/9/pubmed PY - 2013/7/9/medline SP - 1987 EP - 95 JF - Glia JO - Glia VL - 59 IS - 12 N2 - The monocarboxylate transporter MCT4 is a proton-linked carrier particularly important for lactate release from highly glycolytic cells. In the central nervous system, MCT4 is exclusively expressed by astrocytes. Surprisingly, MCT4 expression in primary cultures of mouse cortical astrocytes is conspicuously low, suggesting that an external, nonastrocytic signal is necessary to obtain the observed pattern of expression in vivo. Here, we demonstrate that nitric oxide (NO), delivered by various NO donors, time- and dose-dependently induces MCT4 expression in cultured cortical astrocytes both at the mRNA and protein levels. In contrast, NO does not enhance the expression of MCT1, the other astrocytic monocarboxylate transporter. The transcriptional effect of NO is not mediated by a cGMP-dependent mechanism as shown by the absence of effect of a cGMP analog or of a selective guanylate cyclase inhibitor. NO causes an increase in astrocytic lactate transport capacity which requires the enhancement of MCT4 expression as both are prevented by the use of a specific siRNA against MCT4. In addition, cumulated lactate release by astrocytes over a period of 24 h was also enhanced by NO treatment. Our data suggest that NO represents a putative intercellular signal to control MCT4 expression in astrocytes and in doing so, to facilitate lactate transfer to other surrounding cell types in the central nervous system. © 2011 Wiley-Liss, Inc. SN - 1098-1136 UR - https://www.unboundmedicine.com/medline/citation/21901758/Nitric_oxide_induces_the_expression_of_the_monocarboxylate_transporter_MCT4_in_cultured_astrocytes_by_a_cGMP_independent_transcriptional_activation_ L2 - https://doi.org/10.1002/glia.21240 DB - PRIME DP - Unbound Medicine ER -