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The organic osmolytes betaine and proline are transported by a shared system in early preimplantation mouse embryos

✍ Scribed by Mohamed-Kheir Idris Anas; Mary-Anne Hammer; Michael Lever; Jo-Ann L. Stanton; Jay M. Baltz


Publisher
John Wiley and Sons
Year
2006
Tongue
English
Weight
342 KB
Volume
210
Category
Article
ISSN
0021-9541

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✦ Synopsis


Abstract

Betaine and proline protect preimplantation mouse embryos against increased osmolarity and decreased cell volume, implying that they may function as organic osmolytes. However, the transport system(s) that mediates their accumulation in fertilized eggs and early embryos was unknown, and previously identified mammalian organic osmolyte transporters could not account for their transport. Here, we report that there is a single saturable transport component shared by betaine and proline in 1‐cell mouse embryos. A series of inhibitors had nearly identical effects on both betaine and proline transport by this system. In addition, K~i~ values for reciprocal inhibition of betaine and proline transport were ∼100–300 µM, similar to K~m~ values (∼200–300 µM) for their transport, and both had similar maximal transport rates (V~max~). The K~i~ values for inhibition of betaine and proline transport by dimethylglycine were similar (∼2 mM), further supporting transport of both substrates by a single transport system. Finally, betaine and proline transport each required Na^+^‐ and Cl^−^. These data were consistent with a single, Na^+^‐ and Cl^−^‐requiring, betaine/proline transport system in 1‐cell mouse embryos. While betaine was only transported by a single saturable system, we found an additional, less conspicuous proline transport route that was betaine‐insensitive, Na^+^‐sensitive, and inhibited by alanine, leucine, cysteine, and methionine. Furthermore, we showed that betaine, like proline, is present in the mouse oviduct and thus could serve as a physiological substrate. Finally, accumulation of both betaine and proline increased with increasing osmolarity, consistent with a possible role as organic osmolytes in early embryos. J. Cell. Physiol. 210: 266–277, 2007. © 2006 Wiley‐Liss, Inc.