Kidney-Specific Reduction of Oxidative Phosphorylation Genes Derived from Spontaneously Hypertensive Rat

Authors

Jason A. Collett, University of Kentucky
Jiffin K. Paulose, University of KentuckyFollow
Vincent M. Cassone, University of KentuckyFollow
Jeffrey L. Osborn, University of KentuckyFollow

Abstract

Mitochondrial (Mt) dysfunction contributes to the pathophysiology of renal function and promotes cardiovascular disease such as hypertension. We hypothesize that renal Mt-genes derived from female spontaneously hypertensive rats (SHR) that exhibit hypertension have reduced expression specific to kidney cortex. After breeding a female Okamoto-Aoki SHR (SAP = 188mmHg) with Brown Norway (BN) males (SAP = 100 and 104 mmHg), hypertensive female progeny were backcrossed with founder BN for 5 consecutive generations in order to maintain the SHR mitochondrial genome in offspring that contain over increasing BN nuclear genome. Mt-protein coding genes (13 total) and nuclear transcription factors mediating Mt-gene transcription were evaluated in kidney, heart and liver of normotensive (NT: n = 20) vs. hypertensive (HT: n = 20) BN/SHR-mt^SHR using quantitative real-time PCR. Kidney cortex, but not liver or heart Mt-gene expression was decreased ~2-5 fold in 12 of 13 protein encoding genes of HT BN/SHR-mt^SHR. Kidney cortex but not liver mRNA expression of the nuclear transcription factors Tfam, NRF1, NRF2 and Pgc1α were also decreased in HT BN/SHR-mt^SHR. Kidney cortical tissue of HT BN/SHR-mt^SHR exhibited lower cytochrome oxidase histochemical staining, indicating a reduction in renal oxidative phosphorylation but not in liver or heart. These results support the hypothesis that renal cortex of rats with SHR mitochondrial genome has specifically altered renal expression of genes encoding mitochondrial proteins. This kidney-specific coordinated reduction of mitochondrial and nuclear oxidative metabolism genes may be associated with heritable hypertension in SHR.

Document Type

Article

Publication Date

8-26-2015

Notes/Citation Information

Published in PLOS One, v. 10, no. 8, article e0136441, p. 1-19.

© 2015 Collett et al.

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Digital Object Identifier (DOI)

http://dx.doi.org/10.1371/journal.pone.0136441

Funding Information

This study was supported by the National Science Foundation (NSF) # 437768, the American Heart Association Predoctoral Fellowship awarded to J. A. Collett AHA# 1PRE7100000 and the Gertrude Flora Ribble Research Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Repository Citation

Collett, Jason A.; Paulose, Jiffin K.; Cassone, Vincent M.; and Osborn, Jeffrey L., "Kidney-Specific Reduction of Oxidative Phosphorylation Genes Derived from Spontaneously Hypertensive Rat" (2015). Biology Faculty Publications. 98.
https://uknowledge.uky.edu/biology_facpub/98