Skip to main content

Advertisement

SpringerLink
Log in

Impaired Lung Mitochondrial Respiration Following Perinatal Nicotine Exposure in Rats

  • Published:
Lung Aims and scope Submit manuscript

Abstract

Perinatal smoke/nicotine exposure predisposes to chronic lung disease and morbidity. Mitochondrial abnormalities may contribute as the PPARγ pathway is involved in structural and functional airway deficits after perinatal nicotine exposure. We hypothesized perinatal nicotine exposure results in lung mitochondrial dysfunction that can be rescued by rosiglitazone (RGZ; PPARγ receptor agonist). Sprague–Dawley dams received placebo (CON), nicotine (NIC, 1 mg kg−1), or NIC + RGZ (3 mg kg−1) daily from embryonic day 6 to postnatal day 21. Parenchymal lung (~10 mg) was taken from adult male offspring for mitochondrial assessment in situ. ADP-stimulated O2 consumption was less in NIC and NIC + RGZ compared to CON (F[2,14] = 17.8; 4.5 ± 0.8 and 4.1 ± 1.4 vs. 8.8 ± 2.5 pmol s mg−1; p < 0.05). The respiratory control ratio for ADP, an index of mitochondrial coupling, was reduced in NIC and remediated in NIC + RGZ (F[2,14] = 3.8; p < 0.05). Reduced mitochondrial oxidative capacity and abnormal coupling were evident after perinatal nicotine exposure. RGZ improved mitochondrial function through tighter coupling of oxidative phosphorylation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

References

  1. Surgeon General’s Report (2004) Washington, DC

  2. Mackay J, Ritthiphakdee B, Reddy KS (2013) Tobacco control in Asia. Lancet 381(9877):1581–1587. doi:10.1016/S0140-6736(13)60854-5

    Article  PubMed  Google Scholar 

  3. Crowley RA (2015) Electronic nicotine delivery systems: executive summary of a policy position paper from the American College of Physicians. Ann Intern Med 162(8):583–584. doi:10.7326/M14-2481

    Article  PubMed  Google Scholar 

  4. McGraw D (2015) Current and future trends in electronic cigarette use. Int J Psychiatry Med 48(4):325–332. doi:10.2190/PM.48.4.g

    PubMed  Google Scholar 

  5. Rehan VK, Torday JS (2012) PPARgamma signaling mediates the evolution, development, homeostasis, and repair of the lung. PPAR Res 2012:289867. doi:10.1155/2012/289867

    Article  PubMed  PubMed Central  Google Scholar 

  6. Gong M, Liu J, Sakurai R et al (2015) Perinatal nicotine exposure suppresses PPARgamma epigenetically in lung alveolar interstitial fibroblasts. Mol Genet Metab 114(4):604–612. doi:10.1016/j.ymgme.2015.01.004

    Article  CAS  PubMed  Google Scholar 

  7. Morales E, Sakurai R, Husain S et al (2014) Nebulized PPARgamma agonists: a novel approach to augment neonatal lung maturation and injury repair in rats. Pediatr Res 75(5):631–640. doi:10.1038/pr.2014.8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Liu J, Sakurai R, Rehan VK (2015) PPAR-gamma agonist rosiglitazone reverses perinatal nicotine exposure-induced asthma in rat offspring. Am J Physiol Lung Cell Mol Physiol 308(8):L788–L796. doi:10.1152/ajplung.00234.2014

    Article  CAS  PubMed  Google Scholar 

  9. Liu J, Sakurai R, O’Roark EM et al (2011) PPARgamma agonist rosiglitazone prevents perinatal nicotine exposure-induced asthma in rat offspring. Am J Physiol Lung Cell Mol Physiol 300(5):L710–L717. doi:10.1152/ajplung.00337.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Das KC (2013) Hyperoxia decreases glycolytic capacity, glycolytic reserve and oxidative phosphorylation in MLE-12 cells and inhibits complex I and II function, but not complex IV in isolated mouse lung mitochondria. PLoS One 8(9):e73358. doi:10.1371/journal.pone.0073358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Reiss OK (1966) Studies of lung metabolism. I. Isolation and properties of subcellular fractions from rabbit lung. J Cell Biol 30(1):45–57

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Magnani ND, Marchini T, Tasat DR et al (2011) Lung oxidative metabolism after exposure to ambient particles. Biochem Biophys Res Commun 412(4):667–672. doi:10.1016/j.bbrc.2011.08.021

    Article  CAS  PubMed  Google Scholar 

  13. Pesta D, Gnaiger E (2012) High-resolution respirometry: OXPHOS protocols for human cells and permeabilized fibers from small biopsies of human muscle. Methods Mol Biol 810:25–58. doi:10.1007/978-1-61779-382-0_3

    Article  CAS  PubMed  Google Scholar 

  14. Miglio G, Rosa AC, Rattazzi L et al (2009) PPARgamma stimulation promotes mitochondrial biogenesis and prevents glucose deprivation-induced neuronal cell loss. Neurochem Int 55(7):496–504. doi:10.1016/j.neuint.2009.05.001

    Article  CAS  PubMed  Google Scholar 

  15. Brand MD, Buckingham JA, Esteves TC et al (2004) Mitochondrial superoxide and aging: uncoupling-protein activity and superoxide production. Biochem Soc Symp 71:203–213

    Article  CAS  PubMed  Google Scholar 

Download references

Source of Support

NIH HD51857, HD71731, TRDRP 23RT-0018, DTC supported by Pulmonary Education & Research Foundation.

Author Contributions

DTC, HBR, VKR conceived of and designed experiments. DTC, JL, RS performed the experiments. DTC analyzed the data and prepared figures. All authors interpreted the results. DTC drafted the manuscript. All authors approved the final version.

Author information

Authors and Affiliations

  1. Division of Respiratory & Critical Care Physiology & Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA

    Daniel T. Cannon & Harry B. Rossiter

  2. School of Exercise & Nutritional Sciences, San Diego State University, 5500 Campanile Drive, San Diego, CA, 92182, USA

    Daniel T. Cannon

  3. Division of Neonatology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA

    Jie Liu, Reiko Sakurai & Virender K. Rehan

  4. School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK

    Harry B. Rossiter

Authors
  1. Daniel T. Cannon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jie Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Reiko Sakurai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Harry B. Rossiter
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Virender K. Rehan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniel T. Cannon.

Ethics declarations

Conflict of interest

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cannon, D.T., Liu, J., Sakurai, R. et al. Impaired Lung Mitochondrial Respiration Following Perinatal Nicotine Exposure in Rats. Lung 194, 325–328 (2016). https://doi.org/10.1007/s00408-016-9859-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00408-016-9859-2

Keywords

Search

Navigation