Signaling role of PDE isozymes in pathobiology of glomerular mesangial cells. Studies in vitro and in vivo

Cell Biochemistry and Biophysics
T P Dousa


Mesangial cells (MC) of renal glomeruli respond to immune-inflammatory injury by accelerated proliferation and generation of reactive oxygen metabolites (ROM). We studied in vivo and in vitro roles of cAMP-protein kinase A (PKA) signaling in modulation of these pathobiologic processes with focus on PDE isozymes. Mitogenic synthesis of DNA in mesangial cells grown in primary culture was blocked by forskolin and dibutyryl cyAMP. Incubation of MC with PDE-3 inhibitors, cilostamide and lixazinone, inhibited (> 50%) mitogenesis, whereas inhibitors of PDE-4, rolipram and denbufylline, caused little or no inhibition. Conversely, inhibitors of PDE-4 suppressed generation of ROM in MC, whereas inhibitors of PDE-3 had no effect. Incubation of mesangial cells with cilostamide or with rolipram increased in situ activity of PKA, and effects of the two inhibitors were additive. PDE inhibitors also decreased activity of mitogen-activated protein kinase. The efficacy of PDE isozyme inhibitors (IC50) to suppress mitogenesis or ROM generation paralleled IC50 for inhibition of cAMP hydrolysis by extracts from mesangial cells. Administration of lixazinone or lixazinone in combination with rolipram to rats with mesangial proliferative glomeruloneph...Continue Reading


Aug 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·M L DufauK J Catt
Oct 1, 1989·Physiological Reviews·P MenéM J Dunn
Oct 24, 1995·Biochemical and Biophysical Research Communications·E N ChiniT P Dousa
Sep 10, 1995·Archives of Biochemistry and Biophysics·V C ManganielloE Degerman
Nov 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·L M GravesE G Krebs
Nov 1, 1994·Trends in Biochemical Sciences·G DaumU R Rapp
Jun 1, 1994·Kidney International·R J Johnson
Oct 1, 1994·Molecular and Cellular Biology·S HäfnerW Kolch
Oct 25, 1994·Proceedings of the National Academy of Sciences of the United States of America·T L LetoI de Mendez
Jan 1, 1994·Molecular Endocrinology·J D Scott, S McCartney
Jun 7, 1994·Proceedings of the National Academy of Sciences of the United States of America·H SumimotoK Takeshige
Nov 12, 1993·Science·J Marx
Apr 1, 1996·Current Opinion in Cell Biology·A Levitzki
Aug 1, 1996·Trends in Pharmacological Sciences·T MüllerJ R Fozard
Oct 1, 1996·Molecular and Cellular Biology·H MischakW Kolch
Sep 17, 1996·Proceedings of the National Academy of Sciences of the United States of America·C Y Huang, J E Ferrell
Jan 1, 1997·Journal of Molecular and Cellular Cardiology·T HirozaneS Sasayama
Dec 9, 1997·The Journal of Laboratory and Clinical Medicine·K MatousovicT P Dousa

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