pH-dependent pyridoxine transport by SLC19A2 and SLC19A3: Implications for absorption in acidic microclimates

Area of Science:

• Cell biology
• Molecular biology
• Nutrient transport

Background:

• SLC19A2 and SLC19A3 are known as thiamine transporters (THTR1 and THTR2).
• These transporters import thiamine (vitamin B1) into cells.
• They also transport cationic drugs like metformin, but their substrate specificity for other molecules is not fully understood.

Purpose of the Study:

• To investigate if SLC19A2 and SLC19A3 can transport pyridoxine (vitamin B6).
• To determine the transport characteristics and physiological relevance of pyridoxine uptake mediated by these transporters.

Main Methods:

• Utilized Madin-Darby canine kidney II (MDCKII) and human embryonic kidney 293 (HEK293) cells for transporter expression.
• Employed Caco-2 cells as a model for human intestinal epithelial cells.
• Performed gene silencing using siRNAs to assess endogenous transporter function.

Main Results:

• Stable expression of SLC19A2 and SLC19A3 significantly increased pyridoxine uptake in kidney cells, especially under acidic conditions (pH 5.5).
• Transport was pH-dependent, saturable, protonophore-sensitive, and inhibited by pyridoxine analogs and thiamine.
• Silencing SLC19A3 in Caco-2 cells reduced carrier-mediated pyridoxine uptake.

Conclusions:

• SLC19A2 and SLC19A3 can recognize and transport pyridoxine.
• These transporters operate optimally in acidic environments.
• Suggests a role for SLC19A2 and SLC19A3 in pyridoxine transport in acidic tissues, such as the small intestine.