Interactions between mitochondrial proteins and lipid peroxidation products in the maintenance of the glomerular filtration barrier in the in vitro perfused kidney.
BACKGROUND
The fourth complex of the mitochondrial respiratory chain, cytochrome-c oxidase (CytC) consists of thirteen both mitochondrially and nuclearly encoded subunits, which are differently regulated in proteinuric kidneys. The effect of mitochondrial involvement on proteinuria is not known.


METHODS
We set up an in vitro kidney perfusion model to study the direct effect of inhibitors of the mitochondrial respiratory chain, rotenone and antimycin A, on the glomerular filtration barrier by using immunohistochemistry and Northern blotting and quantitating the resulting proteinuria.


RESULTS
Rapid onset of proteinuria and characteristic changes in CytC subunits were seen in the perfused kidneys. Urinary protein excretion increased significantly in the rotenone- and antimycin-A-treated groups during perfusion. Downregulation of CytC subunits I and IV was similarly found in the groups treated with rotenone and antimycin A, while increases in the lipid peroxidation (LPO) products malondialdehyde and 4-hydroxynonenal which reflect mitochondrial damage, were observed.


CONCLUSIONS
These data show rapid changes in mitochondrial proteins and induction of proteinuria in response to exposure to mitochondrial inhibitors. Together with the concomitant increase in local LPO products, these results suggest that continuous maintenance of a proper energy balance is important to maintain the glomerular filtration barrier.
Wang
S
S
Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Finland.
Solin
M
M
Ahola
H
H
Luimula
P
P
Holthöfer
H
H
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000502:physiology*; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology*; D007678:Kidney Glomerulus / Q000502:physiology*; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010477:Perfusion; D011507:Proteinuria / Q000139:chemically induced; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012402:Rotenone / Q000494:pharmacology
D000447:Aldehydes; D007527:Isoenzymes; D008054:Lipid Peroxides; D012402:Rotenone; D008315:Malondialdehyde; D000968:Antimycin A; D003576:Electron Transport Complex IV; C027576:4-hydroxy-2-nonenal