Adenovirus stimulates choline efflux by increasing expression of organic cation transporter-2.
We examined the effect of wild-type human adenovirus (Ad5) on choline transport in murine lung epithelia (MLE) and in rodent primary alveolar type II cells. Cells were active in pH-sensitive, reversible transport of choline, a process blocked pharmacologically with phenoxybenzamine, an inhibitor of organic cation transporters (OCT). PCR products for the choline transporters, OCT-1 and OCT-2, were detected, but only OCT-2 protein was robustly expressed within MLE and primary alveolar epithelial cells. Ad5 produced a two- to threefold increase in choline efflux from cells, resulting in a significant reduction in intracellular choline content and its major product, phosphatidylcholine. Effects of Ad5 on choline efflux were inhibited with phenoxybenzamine, and choline efflux was attenuated by OCT-2 small interfering RNA. Adenovirus also produced a dose-dependent increase in immunoreactive OCT-2 levels concomitant with increased cellular OCT-2 steady-state mRNA. These results indicate that adenoviruses can significantly disrupt choline trafficking in lung epithelia by upregulating expression of an alveolar protein involved in organic cation transport.
Miakotina
Olga L
OL
Depts. of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
Agassandian
Marianna
M
Shi
Lei
L
Look
Dwight C
DC
Mallampalli
Rama K
RK
D000256:Adenoviridae / Q000502:physiology*; D000257:Adenoviridae Infections / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001682:Biological Availability; D001692:Biological Transport; D002460:Cell Line; D002794:Choline / Q000378:metabolism* / Q000493:pharmacokinetics; D004847:Epithelial Cells / Q000378:metabolism; D015870:Gene Expression; D008168:Lung / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D027701:Organic Cation Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000075102:Organic Cation Transporter 2; D010643:Phenoxybenzamine / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology / Q000821:virology; D051381:Rats; D015854:Up-Regulation
D027701:Organic Cation Transport Proteins; D000075102:Organic Cation Transporter 2; D010713:Phosphatidylcholines; C491012:Slc22a2 protein, mouse; C100590:Slc22a2 protein, rat; C017463:lecithins, disaturated; D010643:Phenoxybenzamine; D002794:Choline