Expression of ammonia transporters, Rhbg and Rhcg, in chronic cyclosporine nephropathy in rats.
OBJECTIVE
Cyclosporine (CsA)-induced renal injury causes renal tubular acidosis. The current study was performed to evaluate the influence of CsA-induced renal injury on the ammonia transporter family members, Rh B-glycoprotein (Rhbg) and Rh C-glycoprotein (Rhcg).


METHODS
Rats were treated daily for 1 or 4 weeks with vehicle (VH) or CsA. Induction of chronic CsA-induced nephropathy was confirmed by demonstrating impaired renal function and characteristic histopathology. Rhbg and Rhcg expression was evaluated with immunoblot, immunohistochemistry, real-time RT-PCR and electron microscopy.


RESULTS
CsA treatment for 4 weeks developed mild metabolic acidosis and decreased urinary ammonia excretion. Rhcg mRNA expression was unchanged in both the cortex and outer medulla, but Rhcg protein expression in the CsA group was significantly reduced in the cortex and outer medulla. There were no significant differences in Rhbg mRNA and protein expression between the CsA and VH group.


CONCLUSIONS
Long-term treatment with CsA in rats results in decreased urinary ammonia excretion accompanied by decreased expression of Rhcg; these changes are likely to mediate the CsA-induced defect in ammonium excretion in the collecting duct.
Lim
Sun Woo
SW
Department of Internal Medicine, Catholic University of Korea, Seoul, Korea.
Ahn
Kyung Ohk
KO
Kim
Wan Young
WY
Han
Dong He
DH
Li
Can
C
Ghee
Jung Yeon
JY
Han
Ki Hwan
KH
Kim
Hye-Young
HY
Handlogten
Mary E
ME
Kim
Jin
J
Yang
Chul Woo
CW
Weiner
I David
ID
D000818:Animals; D027682:Cation Transport Proteins / Q000096:biosynthesis* / Q000187:drug effects*; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D027682:Cation Transport Proteins; D008562:Membrane Glycoproteins; C508142:Rh type B glycoprotein, rat; C508143:Rh type C glycoprotein, rat; D016572:Cyclosporine
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