Neuronal ubiquitin C-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme that maintains intracellular ubiquitin pools and promotes axonal transport. Uchl1 deletion in mice leads to progressive axonal degeneration, affecting the dorsal root ganglion that harbors axons emanating to the kidney. Innervation is a crucial regulator of renal hemodynamics, though the contribution of neuronal UCHL1 to this is unclear. Immunofluorescence revealed significant neuronal UCHL1 expression in mouse kidney, including periglomerular axons. Glomerular filtration rate trended higher in 6-week-old Uchl1-/- mice, and by 12 weeks of age, these displayed significant glomerular hyperfiltration, coincident with the onset of neurodegeneration. Angiotensin converting enzyme inhibition had no effect on glomerular filtration rate of Uchl1-/- mice indicating that the renin–angiotensin system does not contribute to the observed hyperfiltration. DCE-MRI revealed increased cortical renal blood flow in Uchl1-/- mice, suggesting that hyperfiltration results from afferent arteriole dilation. Nonetheless, hyperglycemia, cyclooxygenase-2, and nitric oxide synthases were ruled out as sources of hyperfiltration in Uchl1-/- mice as glomerular filtration rate remained unchanged following insulin treatment, and cyclooxygenase-2 and nitric oxide synthase inhibition. Finally, renal nerve dysfunction in Uchl1-/- mice is suggested given increased renal nerve arborization, decreased urinary norepinephrine, and impaired vascular reactivity. Uchl1-deleted mice demonstrate glomerular hyperfiltration associated with renal neuronal dysfunction, suggesting that neuronal UCHL1 plays a crucial role in regulating renal hemodynamics.
Skip Nav Destination
Article navigation
July 2018
-
Cover Image
Cover Image
The 3D structure of recombinant human deoxyribonuclease I. The N-terminal leucine shown in yellow at the top of the structure was selected for PEGylation of the protein. The amino acids shown in yellow towards the bottom of the protein are those interacting with globular actin, a potent inhibitor of human deoxyribonuclease I; for details, see pages 1439–1452.
Research Article|
July 18 2018
Hyperfiltration in ubiquitin C-terminal hydrolase L1-deleted mice
Naomi C. Boisvert;
Naomi C. Boisvert
1Kidney Research Centre, Ottawa, Ontario, Canada
2Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
Search for other works by this author on:
Chet E. Holterman;
Chet E. Holterman
1Kidney Research Centre, Ottawa, Ontario, Canada
Search for other works by this author on:
Jean-François Thibodeau;
Jean-François Thibodeau
1Kidney Research Centre, Ottawa, Ontario, Canada
2Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
Search for other works by this author on:
Rania Nasrallah;
Rania Nasrallah
2Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
Search for other works by this author on:
Eldjonai Kamto;
Eldjonai Kamto
1Kidney Research Centre, Ottawa, Ontario, Canada
Search for other works by this author on:
Cesar H. Comin;
Cesar H. Comin
3São Carlos Institute of Physics, University of São Paulo, São Carlos, Brazil
Search for other works by this author on:
Luciano da F. Costa;
Luciano da F. Costa
4IFSC, University of São Paulo, São Carlos, Brazil
Search for other works by this author on:
Anthony Carter;
Anthony Carter
2Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
5Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
6Canadian Partnership for Stroke Recovery, Ottawa, Canada
Search for other works by this author on:
Richard L. Hébert;
Richard L. Hébert
2Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
Search for other works by this author on:
Alex Gutsol;
Alex Gutsol
1Kidney Research Centre, Ottawa, Ontario, Canada
Search for other works by this author on:
Gregory O. Cron;
Gregory O. Cron
7The Ottawa Hospital, Ottawa, Ontario, Canada
Search for other works by this author on:
Baptiste Lacoste;
Baptiste Lacoste
2Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
8Neuroscience Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
9Brain and Mind Research Institute, University of Ottawa, Ottawa, Ontario, Canada
Search for other works by this author on:
Douglas A. Gray;
Douglas A. Gray
5Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
10Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
Search for other works by this author on:
Chris R. Kennedy
1Kidney Research Centre, Ottawa, Ontario, Canada
2Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
Correspondence: Chris R. Kennedy ([email protected])
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
January 30 2018
Revision Received:
April 13 2018
Accepted:
May 04 2018
Accepted Manuscript online:
May 08 2018
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Clin Sci (Lond) (2018) 132 (13): 1453–1470.
Article history
Received:
January 30 2018
Revision Received:
April 13 2018
Accepted:
May 04 2018
Accepted Manuscript online:
May 08 2018
Citation
Naomi C. Boisvert, Chet E. Holterman, Jean-François Thibodeau, Rania Nasrallah, Eldjonai Kamto, Cesar H. Comin, Luciano da F. Costa, Anthony Carter, Richard L. Hébert, Alex Gutsol, Gregory O. Cron, Baptiste Lacoste, Douglas A. Gray, Chris R. Kennedy; Hyperfiltration in ubiquitin C-terminal hydrolase L1-deleted mice. Clin Sci (Lond) 18 July 2018; 132 (13): 1453–1470. doi: https://doi.org/10.1042/CS20180085
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Cited By
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() |