Journal Article

Lipoprotein(a) induces glomerular superoxide anion production.

S Greiber, M Kreusel, H Pavenstädt, P Schollmeyer and C Wanner

in Nephrology Dialysis Transplantation

Volume 12, issue 7, pages 1330-1335
Published in print July 1997 | ISSN: 0931-0509
Published online July 1997 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/12.7.1330
Lipoprotein(a) induces glomerular superoxide anion production.

Show Summary Details

Preview

BACKGROUND: Lipoprotein(a) (Lp(a)) is considered to accelerate glomerular injury in various forms of renal disease. Several tissue culture studies suggested that biological effects of Lp(a) are inhibitable by oxygen radical scavengers. Since reactive oxygen metabolites (ROM) are important mediators of renal disease, we studied the effects of native and oxidized Lp(a) on generation of the ROM superoxide anion in isolated glomeruli and compared them with the effects of native (nLDL) and oxidized LDL cholesterol (oxLDL). METHODS: The effect of native and oxidized Lp(a) and LDL on ROM production in isolated rat glomeruli was investigated with a lucigenin chemiluminescence assay. RESULTS: Native Lp(a) caused a moderate, dose dependent stimulation of glomerular ROM production: Maximum ROM production to 159 +/- 9% of control glomeruli was induced by nLp(a) 20 micrograms/ml. Lp(a)-induced chemiluminescence was completely inhibited by the cell permeable oxygen radical scavenger Tiron (10 Mm). Oxidized Lp(a) (20 micrograms/ml) caused a more pronounced stimulation of ROM production to 204 +/- 12% of control values. Interestingly, only oxLDL, but not nLDL had a significant effect on glomerular ROM production (ox LDL 50 micrograms/ml: 192 +/- 19% of control). Lp(a) stimulated ROM production was completely inhibited by the protein kinase C inhibitor bis- indolyl malemide (BIM): BIM 10(-6) M inhibited 52 +/- 3%, BIM 10(-5) M inhibited 94 +/- 5% of Lp(a)-induced ROM production. ROM production was also inhibited, when intracellular CAMP levels were elevated by forskolin. CONCLUSION: Lp(a) and oxLp(a) induce the activation of ROM in glomeruli by a pathway that is sensitive to inhibition of protein kinase C and elevation of intracellular CAMP levels.

Journal Article.  0 words. 

Subjects: Nephrology

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.