Effect of nitric oxide donors on renal tubular epithelial cell-matrix adhesion.
BACKGROUND
Nitric oxide (NO) and its metabolite, peroxynitrite (ONOO-), are involved in renal tubular cell injury. We postulated that if NO/ONOO- has an effect to reduce cell adhesion to the basement membrane, this may contribute to tubular obstruction and may be partially responsible for the harmful effect of NO on the tubular epithelium during acute renal failure (ARF).


METHODS
We examined the effect of the NO donors (z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1- ium-1, 2-diolate (DETA/NO), spermine NONOate (SpNO), and the ONOO- donor 3-morpholinosydnonimine (SIN-1) on cell-matrix adhesion to collagen types I and IV and fibronectin using three renal tubular epithelial cell lines: LLC-PK1, BSC-1, and OK.


RESULTS
In LLC-PK1 cells, DETA/NO (500 microM) had no effect, and SpNO (500 microM) had a modest effect on cell adhesion compared with controls. Exposure to SIN-1 caused a dose-dependent impairment in cell-matrix adhesion. Similar results were obtained in the different cell types and matrix proteins. The effect of SIN-1 (500 microM) on LLC-PK1 cell adhesion was not associated with either cell death or alteration of matrix protein and was attenuated by either the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, the superoxide scavenger superoxide dismutase, or the ONOO- scavenger uric acid in a dose-dependent manner.


CONCLUSIONS
These results therefore support the possibility that ONOO- generated in the tubular epithelium during ischemia/reperfusion has the potential to impair the adhesion properties of tubular cells, which then may contribute to the tubular obstruction in ARF.
Wangsiripaisan
A
A
Department of Medicine, University of Colorado Health Sciences Center, Denver, USA.
Gengaro
P E
PE
Nemenoff
R A
RA
Ling
H
H
Edelstein
C L
CL
Schrier
R W
RW
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002522:Chlorocebus aethiops; D003094:Collagen / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018374:LLC-PK1 Cells; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009566:Nitrates / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009893:Opossums; D013481:Superoxides / Q000494:pharmacology; D013552:Swine
D005353:Fibronectins; D016166:Free Radical Scavengers; D009566:Nitrates; D020030:Nitric Oxide Donors; D013481:Superoxides; C039642:peroxynitric acid; D009569:Nitric Oxide; C002385:linsidomine; D003094:Collagen; D008981:Molsidomine