Characterization of mitochondrial NADH dehydrogenase 1α subcomplex 10 variants in cardiac muscles from normal Wistar rats and spontaneously hypertensive rats: Implications in the pathogenesis of hypertension

Huang,Liying; Jin,Xian; Xia,Li; Wang,Xiaoling; Yu,Yun; Liu,Cunfei; Shao,Dongmin; Fang,Ningyuan; Meng,Chao

doi:10.3892/mmr.2015.4607

Characterization of mitochondrial NADH dehydrogenase 1α subcomplex 10 variants in cardiac muscles from normal Wistar rats and spontaneously hypertensive rats: Implications in the pathogenesis of hypertension

Authors:
- Liying Huang
- Xian Jin
- Li Xia
- Xiaoling Wang
- Yun Yu
- Cunfei Liu
- Dongmin Shao
- Ningyuan Fang
- Chao Meng
View Affiliations

Affiliations: Department of Geriatrics, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, P.R. China, Department of Pathophysiology, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, P.R. China, Section of Vascular Biology, National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK
Published online on: November 23, 2015 https://doi.org/10.3892/mmr.2015.4607
Pages: 961-966

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Mitochondrial dysfunction has been increasingly associated with the development of cardiovascular diseases, including hypertension and cardiac hypertrophy. In the present study, NADH dehydrogenase 1α subcomplex 10 (Ndufa10) was characterized from the left ventricular muscles of spontaneously hypertensive rats (SHRs) and normal Wistar Kyoto (WKY) rats. Western blot analysis demonstrated that there was a shift in the molecular weight (MW) and in the isoelectric point (pI) of the Ndufa10 protein from SHRs and WKY rats. Mass spectrometric analysis revealed that the replacement of an aspartate residue with asparagine at amino acid position 120 was the biochemical difference between the two Ndufa10 isoforms. Further analysis using the bacterially expressed proteins Ndufa10‑120N (WKY) and Ndufa10‑120D (SHR) revealed that the shift in the pI and MW of the two Ndufa10 isoforms was solely caused by the amino acid mutation, and not by post‑translational modifications. Since deficiencies of the mitochondrial complex I are the most common defects in the oxidative phosphorylation system, further studies are required to study the difference between the activities of the two Ndufa10 variants, and their role in the pathogenesis of hypertension.

View Figures

View References

1	Di Lisa F, Canton M, Menabò R, Kaludercic N and Bernardi P: Mitochondria and cardioprotection. Heart Fail Rev. 12:249–260. 2007. View Article : Google Scholar : PubMed/NCBI
2	Lopez-Campistrous A, Hao L, Xiang W, Ton D, Semchuk P, Sander J, Ellison MJ and Fernandez-Patron C: Mitochondrial dysfunction in the hypertensive rat brain: Respiratory complexes exhibit assembly defects in hypertension. Hypertension. 51:412–419. 2008. View Article : Google Scholar : PubMed/NCBI
3	Takimoto E and Kass DA: Role of oxidative stress in cardiac hypertrophy and remodeling. Hypertension. 49:241–248. 2007. View Article : Google Scholar
4	Bernal-Mizrachi C, Gates AC, Weng S, Imamura T, Knutsen RH, DeSantis P, Coleman T, Townsend RR, Muglia LJ and Semenkovich CF: Vascular respiratory uncoupling increases blood pressure and atherosclerosis. Nature. 435:502–506. 2005. View Article : Google Scholar : PubMed/NCBI
5	Smeitink JA, van den Heuvel LW, Koopman WJ, Nijtmans LG, Ugalde C and Willems PH: Cell biological consequences of mitochondrial NADH: Ubiquinone oxidoreductase deficiency. Curr Neurovasc Res. 1:29–40. 2004. View Article : Google Scholar
6	Efremov RG and Sazanov LA: Structure of the membrane domain of respiratory complex I. Nature. 476:414–420. 2011. View Article : Google Scholar : PubMed/NCBI
7	Meng C, Jin X, Xia L, Shen SM, Wang XL, Cai J, Chen GQ, Wang LS and Fang NY: Alterations of mitochondrial enzymes contribute to cardiac hypertrophy before hypertension development in spontaneously hypertensive rats. J Proteome Res. 8:2463–2475. 2009. View Article : Google Scholar : PubMed/NCBI
8	Sardanelli AM, Technikova-Dobrova Z, Scacco SC, Speranza F and Papa S: Characterization of proteins phosphorylated by the cAMP-dependent protein kinase of bovine heart mitochondria. FEBS Lett. 377:470–474. 1995. View Article : Google Scholar : PubMed/NCBI
9	Schulenberg B, Aggeler R, Beechem JM, Capaldi RA and Patton WF: Analysis of steady-state protein phosphorylation in mitochondria using a novel fluorescent phosphosensor dye. J Biol Chem. 278:27251–27255. 2003. View Article : Google Scholar : PubMed/NCBI
10	Schilling B, Aggeler R, Schulenberg B, Murray J, Row RH, Capaldi RA and Gibson BW: Mass spectrometric identification of a novel phosphorylation site in subunit NDUFA10 of bovine mitochondrial complex I. FEBS Lett. 579:2485–2490. 2005. View Article : Google Scholar : PubMed/NCBI
11	Muñoz J, Fernández-Irigoyen J, Santamaría E, Parbel A, Obeso J and Corrales FJ: Mass spectrometric characterization of mitochondrial complex I NDUFA10 variants. Proteomics. 8:1898–1908. 2008. View Article : Google Scholar : PubMed/NCBI
12	Shirai A, Matsuyama A, Yashiroda Y, Hashimoto A, Kawamura Y, Arai R, Komatsu Y, Horinouchi S and Yoshida M: Global analysis of gel mobility of proteins and its use in target identification. J Biol Chem. 283:10745–10752. 2008. View Article : Google Scholar : PubMed/NCBI
13	Lazarou M, McKenzie M, Ohtake A, Thorburn DR and Ryan MT: Analysis of the assembly profiles for mitochondrial- and nuclear-DNA-encoded subunits into complex I. Mol Cell Biol. 27:4228–4237. 2007. View Article : Google Scholar : PubMed/NCBI
14	Distelmaier F, Koopman WJ, van den Heuvel LP, Rodenburg RJ, Mayatepek E, Willems PH and Smeitink JA: Mitochondrial complex I deficiency: From organelle dysfunction to clinical disease. Brain. 132:833–842. 2009. View Article : Google Scholar : PubMed/NCBI
15	Hoefs SJ, van Spronsen FJ, Lenssen EW, Nijtmans LG, Rodenburg RJ, Smeitink JA and van den Heuvel LP: NDUFA10 mutations cause complex I deficiency in a patient with Leigh disease. Eur J Hum Genet. 19:270–274. 2011. View Article : Google Scholar :