Medium osmolarity-dependent biosynthesis of renal cellular sulfoglycolipids is mediated by the MAPK signaling pathway.
Verots S3 and Vero317 cells were shown by metabolic labeling with (35)S-sulfate to contain many more sulfoglycosphingolipids than original Vero cells derived from African green monkey kidney. The activity of galactosyl ceramide sulfotransferase (GST) was shown to be 89- and 92-fold higher in Vero317 cells and Verots S3 cells, respectively, than that of the parent cells, whereas the activity of the degradation enzyme, arylsulfatase A, was unchanged among all the three cell strains. GST gene transcript levels in Verots cells were 14.3-fold higher than those in Vero cells. The cell adhesiveness to the culture plate under hypertonic stress was strengthened significantly in both mutant strains. Among the major sulfoglycolipids of the Verots S3 cell line, assigned as SM4s, SM3, SM2a, and SB1a, the incorporation of (35)S-sulfate into SM3, SM2a and SB1a was upregulated with the increasing tonicity of the medium. Sulfoglycolipids in these renal cells seemed to contribute to the membrane barrier against hypertonic media as shown previously in another renal cell line, MDCK (Niimura and Nagai, 2008). Sulfoglycolipid synthesis was suppressed with the p38 (MAPK) inhibitor SB203580 and/or with the MEK-1/2 (MAPKK) inhibitor PD98059, and with the tyrosine kinase inhibitor genistein, which also reduced the sulfoglycolipid synthesis in a dose-dependent manner. Further the administration of the MAPK/MAPKK inhibitors to the culture medium reduced significantly the viability of Verots S3 cells under hypertonic stress. These findings suggest that sulfoglycolipid synthesis in those renal cells may be regulated to adapt to the renal osmotic circumstances by the medium's osmolarity via the MAPK signaling pathway.
Niimura
Yukio
Y
Research Center of Biomedical Analysis and Radioisotope, Faculty of Medicine, Teikyo University, 2-11-1 Kaga Itabashi-ku, Tokyo, Japan, 173-8605. yniimura@med.teikyo-u.ac.jp
Moue
Toshiko
T
Takahashi
Nobuyoshi
N
Nagai
Ken-ichi
K
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004789:Enzyme Activation / Q000187:drug effects; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006017:Glycolipids / Q000096:biosynthesis*; D006982:Hypertonic Solutions / Q000494:pharmacology; D007553:Isotope Labeling; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007668:Kidney / Q000166:cytology* / Q000201:enzymology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009994:Osmolar Concentration; D009997:Osmotic Pressure / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013312:Stress, Physiological / Q000187:drug effects; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism; D014709:Vero Cells; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D006017:Glycolipids; D006982:Hypertonic Solutions; D047428:Protein Kinase Inhibitors; C011117:sulfoglycolipids; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D015238:Sulfotransferases