Lipoprotein(a) induces glomerular superoxide anion production.
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.


CONCLUSIONS
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.
Greiber
S
S
Department of Medicine, University Hospital of Freiburg, Germany.
Kreusel
M
M
Pavenstädt
H
H
Schollmeyer
P
P
Wanner
C
C
D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism*; D017270:Lipoprotein(a) / Q000494:pharmacology*; D008297:Male; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism*
D017270:Lipoprotein(a); D013481:Superoxides; D000242:Cyclic AMP; D011493:Protein Kinase C