Role of cyclic AMP in idiopathic nephrotic syndrome: a pathway involving a decrease in glomerular cell heparan sulfates?

Autor: Eric Girardin, Béatrice Birmelé, Ariane De Agostini
Rok vydání: 2000
Předmět:
IBMX
Nephrotic Syndrome
Antimetabolites
Phosphodiesterase Inhibitors
Colforsin/pharmacology
Cell
ddc:616.07
Urine
Biochemistry
Rats
Sprague-Dawley
chemistry.chemical_compound
Plasma
Antimetabolites/pharmacology
Urine/physiology
1-Methyl-3-isobutylxanthine
Cyclic AMP
Cyclic AMP/metabolism
Child
Heparitin Sulfate/biosynthesis
Cells
Cultured
1-Methyl-3-isobutylxanthine/pharmacology
ddc:618
Forskolin
Creatinine/metabolism
Mesangial cell
Glomerular basement membrane
Heparan sulfate
Glomerular Mesangium
medicine.anatomical_structure
Child
Preschool
Creatinine
Phosphodiesterase Inhibitors/pharmacology
Plasma/physiology
Signal Transduction
Adult
medicine.medical_specialty
Statistics
Nonparametric
Glomerular Mesangium/metabolism
Internal medicine
medicine
Animals
Humans
Cyclic adenosine monophosphate
Molecular Biology
Dideoxyadenosine/pharmacology
Colforsin
Cell Biology
In vitro
Rats
Nephrotic Syndrome/metabolism
Endocrinology
chemistry
Dideoxyadenosine
Heparitin Sulfate
Zdroj: Journal of Cellular Biochemistry, Vol. 78, No 3 (2000) pp. 363-70
ISSN: 0730-2312
Popis: The physiopathological mechanisms of idiopathic nephrotic syndrome involve a circulating plasma factor and a decrease in HS in the glomerular basement membrane. Previous studies have demonstrated that plasma from patients with INS decreases glomerular cell HS in vitro. We examined the involvement of cyclic adenosine monophosphate (cAMP) in this interaction. We studied the effect of plasma from patients with INS on mesangial cell cAMP. We also determined mesangial cell HS when cAMP levels were modified using a cationic membrane after metabolic labeling. Cellular cAMP levels increased significantly when mesangial cells were incubated with plasma from patients with INS in comparison with control plasma (+77%, P = 0.01). Forskolin and IBMX, which increased cellular cAMP, decreased HS levels (-21 +/- 9% and -15 +/- 6% respectively, P < 0.05 for both), whereas dideoxyadenosine, which decreased cellular cAMP, increased HS levels (+24 +/- 7%, P < 0.05). Plasma from patients with INS decreased glomerular cell HS in comparison with control plasma (-34 +/- 8%, P < 0,05). This effect was abolished when cells were preincubated with ddAdo to prevent an increase in cAMP levels. We conclude that in mesangial cells, plasma from patients with INS increases cAMP levels, and that cAMP mediates a decrease in HS levels. Moreover, the action of plasma from patients on HS was inhibited when an increase in cAMP was prevented. cAMP may therefore be instrumental in the negative effect of the plasma factor on mesangial cell HS.
Databáze: OpenAIRE
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