Title

Splice variants of neuronal nitric oxide synthase are present in the rat kidney

Document Type

Article

Abstract

Background. Decreased renal cortical neuronal NO synthase (nNOS) abundanceactivity correlates with progression of chronic kidney disease (CKD) in a number of animal models.Methods. Western blotting with both N-terminal and C-terminal antibodies, immunoprecipitation, proteomics, RT-PCR and in situ hybridization were used to identify nNOS splice variants in the rat kidney.Results. We have identified two nNOS proteins and transcripts in the rat kidney; nNOSα (∼160 kDa) and nNOSβ (∼140 kDa), a catalytically active exon-2 deletion variant, lacking both the PDZ and protein inhibitor of nNOS (PIN) domains. We also report that nNOSβ protein abundance is increased in the kidney at 11 weeks following 56th nephrectomy (56NX)-induced CKD while nNOSα protein abundance is diminished. The transcript data parallel the protein data in 56NX. By in situ hybridization, there is abundant nNOSα mRNA widely distributed throughout the normal kidney cortex, with very sparse nNOSβ mRNA confined to a few proximal tubules. In a second injury model (6 weeks after 56 renal mass reduction by combined right kidney ablation and infarction of ∼23 of the left kidney; 56 AI), nNOSα mRNA almost disappears from the kidney cortex while nNOSβ mRNA abundance increases in tubules and tubulo-interstitium.Conclusion. The renal cortical nNOSβ protein is present in low abundance in the normal kidney and increases with injury, in an inverse pattern of change with the nNOSα.

Publication Date

5-1-2009

Publication Title

Nephrology Dialysis Transplantation

ISSN

09310509

E-ISSN

14602385

Volume

24

Issue

5

First Page

1422

Last Page

1428

PubMed ID

19073653

Digital Object Identifier (DOI)

10.1093/ndt/gfn676

https://doi.org/10.1093/ndt/gfn676

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