RT Journal Article
SR Electronic
T1 Impact of Inflammation and Infection on the Expression of Amino Acid Transporters in the Placenta: A Minireview
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1251
OP 1258
DO 10.1124/dmd.121.000703
VO 50
IS 9
A1 McColl, Eliza R.
A1 Hurtarte, Milena
A1 Piquette-Miller, Micheline
YR 2022
UL http://dmd.aspetjournals.org/content/50/9/1251.abstract
AB Amino acid transporters expressed in the placenta help to regulate the transfer of amino acids from maternal to fetal circulation. Nutritional or hormonal factors are known to potentially impact the expression of amino acid transporters in the placenta. A relatively new field of inquiry has demonstrated that inflammation, whether associated with infection or not, also alters the expression of amino acid transporters in the placenta. Indeed, studies over the past 15 years have demonstrated that malaria, viral and bacterial models of infection, pre-eclampsia, and direct administration of proinflammatory cytokines can alter placental amino acid transporter expression. Although such studies have largely focused on System A and System L transporters, other transporters are also affected. p38 mitogen-activated protein kinase (p38 MAPK), signal transducer and activator of transcription 3 (STAT3), mammalian target of rapamycin C1 (mTORC1), and AMP-activated protein kinase (AMPK) signaling have all been implicated in these changes, but the underlying mechanisms remain to be fully elucidated. Furthermore, the implications of such changes warrant further investigation. This review will summarize studies that have investigated the impact of inflammation on placental amino acid transporter expression, identify questions that remain unanswered, and propose future areas of research to advance the field. As amino acid transporters are now being considered for drug targeting and drug delivery, furthering our understanding of the regulation of these transporters during disease states will be of increasing clinical value.SIGNIFICANCE STATEMENT Although this is a relatively new field of research, multiple studies have demonstrated that inflammation alters placental amino acid transporter expression. This review will serve to summarize, for the first time, studies in this field and identify gaps in current knowledge as research in this area moves beyond identifying changes in transporter expression to investigating the implications of such changes and the mechanisms underlying them.