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The mitochondria mediate the induction of NOX1 gene expression by aldosterone in an ATF-1-dependent manner

Cellular & Molecular Biology Letters volume 16, pages 226–235 (2011)Cite this article

Abstract

High aldosterone (Ald) levels can induce hypertrophy of vascular smooth muscle cells (VSMCs), which carries high risks of heart failure. A previous study showed that Ald induces hypertrophy of VSMCs by up-regulating NOX1, a catalytic subunit of NADPH oxidase that produces superoxides. However, the precise mechanism remains unknown. Diphenylene iodonium (DPI) is known as an inhibitor of complex I in the mitochondrial respiratory chain, and it was also found to almost completely suppress the induction of NOX1 mRNA and the phosphorylation of activating transcription factor (ATF-1) by PGF2α or PDGF in a rat VSMC cell line. In this study, we found that the Ald-induced phosphorylation of ATF-1 and NOX1 expression was significantly suppressed by DPI. Silencing of ATF-1 gene expression attenuated the induction of NOX1 mRNA expression, and over-expression of ATF-1 restored Ald-induced NOX1 expression. On the basis of this data, we show that the mitochondria mediate aldosterone-induced NOX1 gene expression in an ATF-1-dependent manner.

Abbreviations

ALD:

aldosterone

ATF:

activating transcription factor-1

CRE:

cAMP-response element

CREB:

CRE-binding protein

DMEM:

Dulbecco’s modified Eagle’s medium

DPI:

diphenylene iodonium

FBS:

fetal bovine serum

MnTBAP:

Mn(III)tetrakis(4-benzoic acid)porphyrin chloride

MR:

mineralocorticoid receptor

MTT,3:

(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide

NOX1:

NADPH oxidase 1

ROS:

reactive oxygen species

VSMC:

vascular smooth muscle cell

References

  1. Mazak, I., Fiebeler, A., Muller, D.N., Park, J.K., Shagdarsuren, E., Lindschau, C., Dechend, R., Viedt, C., Pilz, B., Haller, H. and Luft, F.C. Aldosterone potentiates angiotensin II-induced signaling in vascular smooth muscle cells. Circulation 109 (2004) 2792–2800.

    Article  PubMed  CAS  Google Scholar 

  2. Pitt, B., Zannad, F., Remme, W.J., Cody, R., Castaigne, A., Perez, A., Palensky, J. and Wittes, J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure, randomized aldactone evaluation study investigators. N. Engl. J. Med. 341 (1999) 709–717.

    Article  PubMed  CAS  Google Scholar 

  3. Zannad, F., Ella, F., Dousset, B., Perez, A. and Pitt, B. Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the Randomized Aldactone Evaluation Study (RALES), Rales Investigators. Circulation 102 (2000) 2700–2706.

    PubMed  CAS  Google Scholar 

  4. Irani, K. Oxidant signaling in vascular cell growth, death, and survival: a review of the roles of reactive oxygen species in smooth muscle and endothelial cell mitogenic and apoptotic signaling. Circ. Res. 87 (2000) 179–183.

    PubMed  CAS  Google Scholar 

  5. Griendling, K.K., Sorescu, D. and Ushio-Fukai, M. NAD(P)H oxidase: role in cardiovascular biology and disease. Circ. Res. 86 (2000) 449–501.

    Google Scholar 

  6. Suh, Y.A., Arnold, R.S., Lassegue, B., Shi, J., Xu, X., Sorescu, D., Chung, A.B., Griendling, K.K. and Lambeth, J.D. Cell.transformation by the superoxide-generating oxidase Mox1. Nature 401 (1999) 79–82.

    Article  PubMed  CAS  Google Scholar 

  7. Lassegue, B., Sorescu, D., Szocs, K., Yin, Q., Akers, M., Zhang, Y., Grant, S.L., Lambeth, J.D. and Griendling, K.K. Griendling, Novel gp91(phox) homologues in vascular smooth muscle cells: nox1 mediates angiotensin II-induced superoxide formation and redox-sensitive signaling pathways. Circ. Res. 88 (2001) 858–860.

    Article  Google Scholar 

  8. Katsuyama, M., Fan, C., Arakawa, N., Nishinaka, T., Miyagishi, M., Taira, K. and Yabe-Nishimura, C. Essential role of ATF-1 in induction of NOX1, a catalytic subunit of NADPH oxidase: involvement of mitochondrial respiratory chain. Biochem. J. 386 (2005) 255–261.

    Article  PubMed  CAS  Google Scholar 

  9. Matsuno, K., Yamada, H., Iwata, K., Jin, D., Katsuyama, M., Matsuki, M., Takai, S., Yamanish, K., Miyazaki, M., Matsubara, H. and Yabe-Nishimur, C. A Nox1 is involved in angiotensin II-mediated hypertension: a study in Nox1-deficient mice. Circulation 112 (2005) 2677–2685.

    Article  PubMed  CAS  Google Scholar 

  10. Nishinaka, T. and Yabe-Nishimura, C. EGF receptor-ERK pathway is the major signaling pathway that mediates upregulation of aldose reductase expression under oxidative stress. Free Radic. Biol. Med. 31 (2001) 205–216.

    Article  PubMed  CAS  Google Scholar 

  11. Miyagishi, M. and Taira, K. U6 promoter-driven siRNAs with four uridine 3’overhangs efficiently suppress targeted gene expression in mammalian cells. Nat. Biotechnol. 20 (2002) 497–500.

    Article  PubMed  CAS  Google Scholar 

  12. Yokota, T., Sakamoto, N., Enomoto, N., Tanabe, Y., Miyagishi, M., Maekawa, S., Yi, L., Kurosaki, M., Taira, K., Watanabe, M. and Mizusawa, H. Inhibition of intracellular hepatitis C virus replication by synthetic and vector-derived small interfering RNAs. EMBO. Rep. 4 (2003) 602–608.

    Article  PubMed  CAS  Google Scholar 

  13. Li, Y. and Trush, M.A. Diphenyleneiodonium, an NAD(P)H oxidase inhibitor, also potently inhibits mitochondrial reactive oxygen species production. Biochem. Biophys. Res. Commun. 253 (1998) 295–299.

    Article  PubMed  CAS  Google Scholar 

  14. Montminy, M.R., Sevarino, K.A., Wagner, J.A., Mandel, G.. and Goodman, R.H. Identification of a cyclic-AMP-responsive element within the rat somatostatin gene. Proc. Natl. Acad. Sci. USA 83 (1986) 6682–6686.

    Article  PubMed  CAS  Google Scholar 

  15. Katsuyama, M., Fan, C. and Yabe-Nishimura, C. NADPH oxidase is involved in prostaglandin F2alpha-induced hypertrophy of vascular smooth muscle cells: induction of NOX1 by PGF2alpha. J. Biol. Chem. 277 (2002) 13438–13442.

    Article  PubMed  CAS  Google Scholar 

  16. Katsuyama, M., Cevik, M.O., Arakawa, N., Kakehi, T., Nishinaka, T., Iwata, K., Ibi, M., Matsuno K. and Nishimura, C.Y. Myocyte enhancer factor 2B is involved in the inducible expression of NOX1/NADPH oxidase, a vascular superoxide-producing enzyme. FEBS J. 274 (2007) 5128–5136.

    Article  PubMed  CAS  Google Scholar 

  17. Lee, S.B., Bae, I.H., Bae, Y.S. and Um, H.D. Link between mitochondria and NADPH oxidase 1 isozyme for the sustained production of reactive oxygen species and cell death. J. Biol. Chem. 281 (2006) 36228–36235.

    Article  PubMed  CAS  Google Scholar 

  18. Young, M. and Funder, J. Mineralocorticoid action and sodium-hydrogen exchange: studies in experimental cardiac fibrosis Endocrinology 144 (2003) 3848–3851.

    Article  PubMed  CAS  Google Scholar 

  19. Lombes, M., Oblin, M.E., Gasc, J.M., Baulieu, E.E., Farman, N. and Bonvalet, J.P. Immunohistochemical and biochemical evidence for a cardiovascular mineralocorticoid receptor. Circ. Res. 71 (1992) 503–510.

    PubMed  CAS  Google Scholar 

  20. Arriza, J.L., Weinberger, C., Cerelli, G., Glaser, T.M., Handelin B.L., Housman, D.E. and Evans, R.M. Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor. Science 237 (1987) 268–275.

    Article  PubMed  CAS  Google Scholar 

  21. Losel, R.M., Feuring, M., Falkenstein, E. and Wehling, M. Nongenomic effects of aldosterone: cellular aspects and clinical implications. Steroids 67 (2002) 493–498.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Nephrology, West China Hospital of Sichuan University, Guoxue Lane 37, WuHou Zone, Chengdu, 610041, China

    Yanping Fu, Qing Tian, Linlin Yue, Qinjie Xia & Chunyuan Fan

  2. State Key Laboratory of Biotherapy, SiChuan University, 1 Keyuan Road 4, GaoPeng Street, High Technological Development Zone, Chengdu, 610041, China

    Gang Shi

  3. The Second Out-Patient Institutions of the Chengdu Military Region, Chengdu, 610041, China

    Yong Wu

  4. Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan

    Yasuyuki Kawai & Isamu Miyamori

  5. The Second People’s Hospital in Chengdu, Chengdu, 610041, China

    Chunyuan Fan

Authors
  1. Yanping Fu
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  2. Gang Shi
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  3. Yong Wu
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  4. Yasuyuki Kawai
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  5. Qing Tian
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  6. Linlin Yue
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  7. Qinjie Xia
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  8. Isamu Miyamori
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  9. Chunyuan Fan
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Corresponding author

Correspondence to Chunyuan Fan.

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These authors contributed equally to this work

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Fu, Y., Shi, G., Wu, Y. et al. The mitochondria mediate the induction of NOX1 gene expression by aldosterone in an ATF-1-dependent manner. Cell Mol Biol Lett 16, 226–235 (2011). https://doi.org/10.2478/s11658-011-0002-3

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  • DOI: https://doi.org/10.2478/s11658-011-0002-3

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Cellular & Molecular Biology Letters

ISSN: 1689-1392

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