Premium
Identification of Gpdp5 as a glycerophosphocholine phosphodiesterase (GPC‐PDE) involved in osmotic regulation of GPC.
Author(s) -
gallazzini morgan,
Ferraris Joan D,
Burg Maurice B
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a962-d
Subject(s) - chemistry , messenger rna , urea , phosphatidylcholine , osmolyte , phosphodiesterase , biochemistry , microbiology and biotechnology , phospholipid , enzyme , biology , gene , membrane
GPC is an abundant renal medullary organic osmolyte. We previously found that its synthesis from phosphatidylcholine is catalyzed by tonicity‐regulated activity of the phospholipase B, NTE (PNAS 103:, 2006). We also found that its degradation is catalyzed by a GPC‐PDE activity that is inhibited by high NaCl or high urea, contributing to the resultant increase of GPC. We have now identified a specific GPC‐PDE that is inhibited by high NaCl, resulting in increased GPC. In the present studies we found that high NaCl causes a 2.5‐fold increase of GPC in mIMCD3 cells within 24hours. mRNA abundance of Gdpd5 decreases by 70% within 8 hours after adding NaCl. In normotonic medium a specific siRNA against Gdpd5 decreases its mRNA expression by 55% while increasing GPC by 60%. High urea also increases GPC in these cells, but does not affect Gdpd5 mRNA expression, leaving the mechanism unexplained for now. We conclude that Gdpd5 degrades cellular GPC and that inhibition of Gdpd5 is involved in tonicity‐induced accumulation of GPC.