Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
September-2016 Volume 14 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
September-2016 Volume 14 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

The pro-oxidant gene p66shc increases nicotine exposure-induced lipotoxic oxidative stress in renal proximal tubule cells

  • Authors:
    • Istvan Arany
    • Samuel Hall
    • Dustin K. Reed
    • Mehul Dixit
  • View Affiliations / Copyright

    Affiliations: Department of Pediatrics, Division of Pediatric Nephrology, University of Mississippi Medical Center, Jackson, MS 39216, USA
  • Pages: 2771-2777
    |
    Published online on: July 25, 2016
       https://doi.org/10.3892/mmr.2016.5543
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Nicotine (NIC) exposure augments free fatty acid (FFA) deposition and oxidative stress, with a concomitant increase in the expression of the pro-oxidant p66shc. In addition, a decrease in the antioxidant manganese superoxide dismutase (MnSOD) has been observed in the kidneys of mice fed a high‑fat diet. The present study aimed to determine whether the pro‑oxidant p66shc mediates NIC‑dependent increases in renal oxidative stress by augmenting the production of reactive oxygen species (ROS) and suppressing the FFA‑induced antioxidant response in cultured NRK52E renal proximal tubule cells. Briefly, NRK52E renal proximal tubule cells were treated with 200 µM NIC, 100 µM oleic acid (OA), or a combination of NIC and OA. The expression levels of p66shc and MnSOD were modulated according to genetic methods. ROS production and cell injury, in the form of lactate dehydrogenase release, were subsequently detected. Promoter activity of p66shc and MnSOD, as well as forkhead box (FOXO)‑dependent transcription, was investigated using reporter luciferase assays. The results demonstrated that NIC exacerbated OA‑mediated intracellular ROS production and cell injury through the transcriptional activation of p66shc. NIC also suppressed OA‑mediated induction of the antioxidant MnSOD promoter activity through p66shc‑dependent inactivation of FOXO activity. Overexpression of p66shc and knockdown of MnSOD had the same effect as treatment with NIC on OA‑mediated lipotoxicity. These data may be used to generate a therapeutic means to ameliorate renal lipotoxicity in obese smokers.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Schaffer JE: Lipotoxicity: When tissues overeat. Curr Opin Lipidol. 14:281–287. 2003. View Article : Google Scholar : PubMed/NCBI

2 

Inoguchi T, Li P, Umeda F, Yu HY, Kakimoto M, Imamura M, Aoki T, Etoh T, Hashimoto T, Naruse M, et al: High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes. 49:1939–1945. 2000. View Article : Google Scholar : PubMed/NCBI

3 

Weinberg JM: Lipotoxicity. Kidney Int. 70:1560–1566. 2006. View Article : Google Scholar

4 

Albanes D, Jones DY, Micozzi MS and Mattson ME: Associations between smoking and body weight in the US population: Analysis of NHANES II. Am J Public Health. 77:439–444. 1987. View Article : Google Scholar : PubMed/NCBI

5 

Chiolero A, Faeh D, Paccaud F and Cornuz J: Consequences of smoking for body weight, body fat distribution, and insulin resistance. Am J Clin Nutr. 87:801–809. 2008.PubMed/NCBI

6 

Hukkanen J, Jacob P III and Benowitz NL: Metabolism and disposition kinetics of nicotine. Pharmacol Rev. 57:79–115. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Schluger NW: The electronic cigarette: A knight in shining armour or a Trojan horse? Psychiatr Bull (2014). 38:201–203. 2014. View Article : Google Scholar

8 

Jaimes EA, Tian RX and Raij L: Nicotine: The link between cigarette smoking and the progression of renal injury? Am J Physiol Heart Circ Physiol. 292:H76–H82. 2007. View Article : Google Scholar

9 

Orth SR, Viedt C and Ritz E: Adverse effects of smoking in the renal patient. Tohoku J Exp Med. 194:1–15. 2001. View Article : Google Scholar : PubMed/NCBI

10 

Arany I, Hall S, Reed DK, Reed CT and Dixit M: Nicotine enhances high-fat diet-induced oxidative stress in the kidney. Nicotine Tob Res. 18:1628–1634. 2016. View Article : Google Scholar

11 

Arany I, Clark J, Reed DK and Juncos LA: Chronic nicotine exposure augments renal oxidative stress and injury through transcriptional activation of p66shc. Nephrol Dial Transplant. 28:1417–1425. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Arany I, Clark JS, Reed DK, Juncos LA and Dixit M: Role of p66shc in renal toxicity of oleic acid. Am J Nephrol. 38:226–232. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Genestra M: Oxyl radicals, redox-sensitive signalling cascades and antioxidants. Cell Signal. 19:1807–1819. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Koch OR, Fusco S, Ranieri SC, Maulucci G, Palozza P, Larocca LM, Cravero AA, Farre' SM, De Spirito M, Galeotti T and Pani G: Role of the life span determinant P66(shcA) in ethanol-induced liver damage. Lab Invest. 88:750–760. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Pani G and Galeotti T: Role of MnSOD and p66shc in mitochondrial response to p53. Antioxid Redox Signal. 15:1715–1727. 2011. View Article : Google Scholar

16 

Guo J, Gertsberg Z, Ozgen N and Steinberg SF: p66Shc links alpha1-adrenergic receptors to a reactive oxygen species-dependent AKT-FOXO3A phosphorylation pathway in cardiomyocytes. Circ Res. 104:660–669. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Arany I, Faisal A, Clark JS, Vera T, Baliga R and Nagamine Y: p66SHC-mediated mitochondrial dysfunction in renal proximal tubule cells during oxidative injury. Am J Physiol Renal Physiol. 298:F1214–F1221. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Arany I, Faisal A, Nagamine Y and Safirstein RL: p66shc inhibits pro-survival epidermal growth factor receptor/ERK signaling during severe oxidative stress in mouse renal proximal tubule cells. J Biol Chem. 283:6110–6117. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Arany I, Grifoni S, Clark JS, Csongradi E, Maric C and Juncos LA: Chronic nicotine exposure exacerbates acute renal ischemic injury. Am J Physiol Renal Physiol. 301:F125–F133. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Kim CS, Jung SB, Naqvi A, Hoffman TA, DeRicco J, Yamamori T, Cole MP, Jeon BH and Irani K: p53 impairs endothelium-dependent vasomotor function through transcriptional upregulation of p66shc. Circ Res. 103:1441–1450. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Essers MA, Weijzen S, de Vries-Smits AM, Saarloos I, de Ruiter ND, Bos JL and Burgering BM: FOXO transcription factor activation by oxidative stress mediated by the small GTPase Ral and JNK. EMBO J. 23:4802–4812. 2004. View Article : Google Scholar : PubMed/NCBI

22 

Brenkman AB, van den Broek NJ, de Keizer PL, van Gent DC and Burgering BM: The DNA damage repair protein Ku70 interacts with FOXO4 to coordinate a conserved cellular stress response. FASEB J. 24:4271–4280. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Kops GJ, Dansen TB, Polderman PE, Saarloos I, Wirtz KW, Coffer PJ, Huang TT, Bos JL, Medema RH and Burgering BM: Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress. Nature. 419:316–321. 2002. View Article : Google Scholar : PubMed/NCBI

24 

Wahba IM and Mak RH: Obesity and obesity-initiated metabolic syndrome: Mechanistic links to chronic kidney disease. Clin J Am Soc Nephrol. 2:550–562. 2007. View Article : Google Scholar : PubMed/NCBI

25 

Gunta SS and Mak RH: Is obesity a risk factor for chronic kidney disease in children? Pediatr Nephrol. 28:1949–1956. 2013. View Article : Google Scholar

26 

Savino A, Pelliccia P, Chiarelli F and Mohn A: Obesity-related renal injury in childhood. Horm Res Paediatr. 73:303–311. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Hall AM and Unwin RJ: The not so 'mighty chondrion': Emergence of renal diseases due to mitochondrial dysfunction. Nephron Physiol. 105:p1–p10. 2007. View Article : Google Scholar

28 

Lemasters JJ, Nieminen AL, Qian T, Trost LC, Elmore SP, Nishimura Y, Crowe RA, Cascio WE, Bradham CA, Brenner DA and Herman B: The mitochondrial permeability transition in cell death: A common mechanism in necrosis, apoptosis and autophagy. Biochim Biophys Acta. 1366:177–196. 1998. View Article : Google Scholar : PubMed/NCBI

29 

Gray DS, Takahashi M, Bauer M and Bray GA: Changes in individual plasma free fatty acids in obese females during fasting and refeeding. Int J Obes. 15:163–168. 1991.PubMed/NCBI

30 

Craig WY, Palomaki GE and Haddow JE: Cigarette smoking and serum lipid and lipoprotein concentrations: An analysis of published data. BMJ. 298:784–788. 1989. View Article : Google Scholar : PubMed/NCBI

31 

Orth SR and Hallan SI: Smoking: A risk factor for progression of chronic kidney disease and for cardiovascular morbidity and mortality in renal patients-absence of evidence or evidence of absence? Clin J Am Soc Nephrol. 3:226–236. 2008. View Article : Google Scholar

32 

Moyad MA: Obesity, interrelated mechanisms, and exposures and kidney cancer. Semin Urol Oncol. 19:270–279. 2001.

33 

Sinha-Hikim I, Friedman TC, Shin CS, Lee D, Ivey R and Sinha-Hikim AP: Nicotine in combination with a high-fat diet causes intramyocellular mitochondrial abnormalities in male mice. Endocrinology. 153:865–872. 2014. View Article : Google Scholar

34 

Friedman TC, Sinha-Hikim I, Parveen M, Najjar SM, Liu Y, Mangubat M, Shin CS, Lyzlov A, Ivey R, Shaheen M, et al: Additive effects of nicotine and high-fat diet on hepatic steatosis in male mice. Endocrinology. 153:5809–5820. 2012. View Article : Google Scholar : PubMed/NCBI

35 

Brezniceanu ML, Liu F, Wei CC, Chénier I, Godin N, Zhang SL, Filep JG, Ingelfinger JR and Chan JS: Attenuation of interstitial fibrosis and tubular apoptosis in db/db transgenic mice overexpressing catalase in renal proximal tubular cells. Diabetes. 57:451–459. 2008. View Article : Google Scholar

36 

Huang RC, Garratt ES, Pan H, Wu Y, Davis EA, Barton SJ, Burdge GC, Godfrey KM, Holbrook JD and Lillycrop KA: Genome-wide methylation analysis identifies differentially methylated CpG loci associated with severe obesity in childhood. Epigenetics. 10:995–1005. 2015. View Article : Google Scholar : PubMed/NCBI

37 

Lauterstein D, Hoshino R, Gordon T, Watkins BX, Weitzman M and Zelikoff J: The changing face of tobacco use among United States youth. Curr Drug Abuse Rev. 7:29–43. 2014. View Article : Google Scholar : PubMed/NCBI

38 

Grana R, Benowitz N and Glantz SA: E-cigarettes: A scientific review. Circulation. 129:1972–1986. 2014. View Article : Google Scholar : PubMed/NCBI

39 

Baeza-Loya S, Viswanath H, Carter A, Molfese DL, Velasquez KM, Baldwin PR, Thompson-Lake DG, Sharp C, Fowler JC, De La Garza R II and Salas R: Perceptions about e-cigarette safety may lead to e-smoking during pregnancy. Bull Menninger Clin. 78:243–252. 2014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Arany I, Hall S, Reed DK and Dixit M: The pro-oxidant gene p66shc increases nicotine exposure-induced lipotoxic oxidative stress in renal proximal tubule cells. Mol Med Rep 14: 2771-2777, 2016.
APA
Arany, I., Hall, S., Reed, D.K., & Dixit, M. (2016). The pro-oxidant gene p66shc increases nicotine exposure-induced lipotoxic oxidative stress in renal proximal tubule cells. Molecular Medicine Reports, 14, 2771-2777. https://doi.org/10.3892/mmr.2016.5543
MLA
Arany, I., Hall, S., Reed, D. K., Dixit, M."The pro-oxidant gene p66shc increases nicotine exposure-induced lipotoxic oxidative stress in renal proximal tubule cells". Molecular Medicine Reports 14.3 (2016): 2771-2777.
Chicago
Arany, I., Hall, S., Reed, D. K., Dixit, M."The pro-oxidant gene p66shc increases nicotine exposure-induced lipotoxic oxidative stress in renal proximal tubule cells". Molecular Medicine Reports 14, no. 3 (2016): 2771-2777. https://doi.org/10.3892/mmr.2016.5543
Copy and paste a formatted citation
x
Spandidos Publications style
Arany I, Hall S, Reed DK and Dixit M: The pro-oxidant gene p66shc increases nicotine exposure-induced lipotoxic oxidative stress in renal proximal tubule cells. Mol Med Rep 14: 2771-2777, 2016.
APA
Arany, I., Hall, S., Reed, D.K., & Dixit, M. (2016). The pro-oxidant gene p66shc increases nicotine exposure-induced lipotoxic oxidative stress in renal proximal tubule cells. Molecular Medicine Reports, 14, 2771-2777. https://doi.org/10.3892/mmr.2016.5543
MLA
Arany, I., Hall, S., Reed, D. K., Dixit, M."The pro-oxidant gene p66shc increases nicotine exposure-induced lipotoxic oxidative stress in renal proximal tubule cells". Molecular Medicine Reports 14.3 (2016): 2771-2777.
Chicago
Arany, I., Hall, S., Reed, D. K., Dixit, M."The pro-oxidant gene p66shc increases nicotine exposure-induced lipotoxic oxidative stress in renal proximal tubule cells". Molecular Medicine Reports 14, no. 3 (2016): 2771-2777. https://doi.org/10.3892/mmr.2016.5543
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team