Involvement of monocarboxylate transporter 1 (SLC16A1) in the uptake of L-lactate in human astrocytes

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Abstract

Purpose:

Astrocytes, the most abundant glial cells in the central nervous system (CNS), help neurons survive. Monocarboxylate transporters (MCTs) are reported to transport L-lactate, which is important for CNS physiology and cognitive function. However, it remains unclear which MCT isoform is functionally expressed by human astrocytes. The aim of this study was to establish the contribution of each MCT isoform to L-lactate transport in human astrocytes.

Methods:

The function of L-lactate transport was studied using NHA cells as a human astrocyte model and radiolabeled L-lactate. The expression of MCT in human astrocytes was detected by immunohistochemistry staining.

Results:

The cellular uptake of L-lactate was found to be pH- and concentration-dependent with a Km value for L-lactate uptake of 0.64 mM. This Km was similar to what has been previously established for MCT1-mediated L-lactate uptake. α-Cyano-4- hydroxycinnamate (CHC) and 5-oxoproline, which are both MCT1 inhibitors, were found to significantly inhibit the uptake of L-lactate, suggesting MCT1 is primarily responsible for L-lactate transport. Moreover, MCT1 protein was expressed in human astrocytes.

Conclusion:

pH-dependent L-lactate transport is mediated by MCT1 in human astrocytes.

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