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A Rapid and Specific Microplate Assay for the Determination of Intra- and Extracellular Ascorbate in Cultured Cells
Published on: April 11, 2014
Macrophage differentiation increases expression of the ascorbate transporter (SVCT2)
1Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-6303, USA.
Free Radical Biology & Medicine
|February 24, 2009
Summary
Macrophage differentiation enhances vitamin C (ascorbic acid) uptake via increased transporter SVCT2 expression. Ascorbate presence during differentiation boosts this process, involving pathways like PKC and MAP kinase.
Area of Science:
- Cell Biology
- Biochemistry
- Immunology
Background:
- Macrophage differentiation is a critical process in immunity.
- Vitamin C (ascorbic acid) plays a role in cellular functions.
- The role of vitamin C transporters in monocyte-macrophage differentiation is not fully understood.
Purpose of the Study:
- To investigate the role of the vitamin C transporter SVCT2 in macrophage differentiation.
- To determine if vitamin C uptake increases during monocyte-to-macrophage differentiation.
- To elucidate the molecular pathways regulating SVCT2 expression during differentiation.
Main Methods:
- Human THP-1 monocytes were induced to differentiate into macrophages using phorbol 12-myristate 13-acetate (PMA).
- SVCT2 mRNA, protein expression, and function were assessed.
- Inhibitors of protein kinase C (PKC), MAP kinase pathway (MEK/ERK), NF-kappaB, and NADPH oxidase were used to probe signaling pathways.
Main Results:
- PMA treatment significantly increased SVCT2 mRNA, protein levels, and function.
- Ascorbate presence during PMA-induced differentiation inhibited SVCT2 protein increase but enhanced differentiation.
- PKCbetaI/II and the classical MAP kinase pathway (MEK/ERK) were crucial for PMA-induced SVCT2 protein expression.
- NF-kappaB, NADPH oxidase, and antioxidants also influenced SVCT2 transcription, indicating diverse regulatory routes.
Conclusions:
- Monocyte-macrophage differentiation is enhanced by vitamin C (ascorbic acid).
- This process is associated with increased SVCT2 expression and function.
- The regulation of SVCT2 involves sustained activation of PKCbetaI/II, MAP kinase, NADPH oxidase, and NF-kappaB pathways.
