Skip to main content

Advertisement

Log in

The Correlation Between PINK-1/Parkin Mediated Mitophagy, Endoplasmic Reticulum Stress and Total Polyamines in Pediatric Bronchial Asthma: An Integrated Network of Pathways

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Background

Pediatric bronchial asthma signifies a frequent chronic inflammatory airway disorder influencing many children. Despite its irrefutable importance, its exact pathogenesis is not completely elucidated.

Aim of the Study

The study aimed to investigate the correlation between mitophagy machinery proteins, ER stress biomarkers and total polyamine and their role in disease progression via targeting NF-κB mechanisms.

Methods

Sixty children with atopic bronchial asthma were enrolled in the study, they were allocated into 2 equal groups (mild/moderate and severe atopic asthmatic groups). Thirty age-matched healthy control subjects were also included in the study to represent the control group. Phosphatase and tensin homolog (PTEN)-induced kinase-1 (PINK-1) and Parkin messenger RNA (mRNA) expressions were assessed by (RT‐PCR) technique. Levels of inositol requiring enzyme 1α (IRE1α), total polyamines, interleukin 6 & 8 (IL-6, IL-8) and nuclear factor kappa B (NF-κB) were assessed by enzyme‐linked immunosorbent assay. Oxidative stress (OS) biomarkers were also measured.

Results

PINK-1 and PARK mRNA expressions were significantly upregulated in asthmatic patients. Likewise, the level of IRE1α, total polyamines, inflammatory cytokines, and OS biomarkers were significantly elevated in asthmatic groups comparing to control group with the highest levels noticed in severe atopic asthmatic group.

Conclusion

the study documented a correlation between mitophagy machinery proteins, ER stress biomarkers and total polyamines that may pave a new platform to understand pediatric asthma pathogenesis and could be used as reliable biomarkers to evaluate disease progression.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

References

  1. Wenzel SE (2012) Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med 18:716–725

    Article  CAS  Google Scholar 

  2. GINA Report (2011) Global Strategy for Asthma Management and Prevention. http://www.ginasthma.org/.

  3. Holgate ST (2012) Innate and adaptive immune responses in asthma. Nat Med 18:673–683

    Article  CAS  Google Scholar 

  4. Park IH, Um JY, Cho JS, Lee SH, Lee HM (2014) Histamine promotes the release of interleukin-6 via the H1R/p38 and NF-κB pathways in nasal fibroblasts. Allergy Asthma Immunol Res 6:567–572

    Article  CAS  Google Scholar 

  5. Djavaheri-Mergny M, Amelotti M, Mathieu J, Besançon F, Bauvy C, Codogno P (2014) Regulation of autophagy by NFkB transcription factor and reactive oxygen species. Autophagy 3(4):390–392

    Article  Google Scholar 

  6. Fisher L, Soomets U, Toro VC, Chilton L, Jiang Y, Langeland U, Iverfeldt K (2004) Cellular delivery of a double-stranded oligonucleotide NFkB decoy by hybridization to complementary PNA linked to a cell-penetrating peptide. Gene Ther 11:1264–1272

    Article  CAS  Google Scholar 

  7. Babusikova E, Jurecekova J, Evinova A, Jesenak M (2012) Oxidative damage and bronchial asthma. In: Ghanei M (ed) Respiratory deceases. InTech, Rijeka, pp 151–176

    Google Scholar 

  8. Milos J, Maria Zelieskova Z, Babusikova E (2017) Oxidative stress and bronchial asthma in children—causes or consequences? Front Pediatric 5:126–135

    Article  Google Scholar 

  9. Prakash YS, Pabelick CM, Sieck GC (2017) Mitochondrial dysfunction in airway disease. Chest 3:618–626

    Article  Google Scholar 

  10. Manevskia M, Muthumalage T, Devadoss D, Sundar IK, Wang Q et al (2020) Cellular stress responses and dysfunctional Mitochondrial–cellular senescence, and therapeutics in chronic respiratory diseases. Redox Biol 33:101443

    Article  Google Scholar 

  11. Chen A, Burr L, McGuckin M (2018) Oxidative and ER stress in respiratory disease. Clin Transl Immunol 7:1019

    Article  Google Scholar 

  12. Minois N, Carmona-Gutierrez D, Madeo F (2011) Polyamines in aging and disease. Aging 3:716–732

    Article  Google Scholar 

  13. Hoet PH, Nemery B (2000) Polyamines in the lung: polyamine uptake and polyamine-linked pathological or toxicological conditions. Am J Physiol Lung Cell Mol Physiol 278:17–33

    Article  Google Scholar 

  14. Jain V (2018) Role of polyamines in asthma pathophysiology. Med Sci 6:4

    Google Scholar 

  15. Bousquet J, Clark TJH, Hurd S, Khaltaev N, Lenfant C, O’byrne P, Sheffer A (2007) GINA guidelines on asthma and beyond. Allergy 62:102–112

    CAS  PubMed  Google Scholar 

  16. Brown WG, Halonen MJ, Kaltenborn WT, Barbee RA (1979) The relationship of respiratory allergy, skin test reactivity, and serum IgE in a community population sample. J Allergy Clin Immunol 63:328–335

    Article  CAS  Google Scholar 

  17. Crapo RO, Standardization of spirometry, (1994) update. Am J Respir Crit Care Med 152(1995):1107–1136

    Google Scholar 

  18. Sikka M, Tandon R, Rusia U, Madan N (2007) Validation of ESR analyzer using Westergren ESR method. Indian J Pathol Microbiol 50:634–635

    PubMed  Google Scholar 

  19. Burrows B, Hasan FM, Barbee RA, Halonen M, Lebowitz MD (1980) Epidemiologic observations on eosinophilia and its relation to respiratory disorders. Am Rev Respir Dis 122:709–719

    Article  CAS  Google Scholar 

  20. Blandin C, Gausson V, Latscha B (2004) Biochemical and spectrophotometric significance of advanced oxidized protein products. Biochim Biophys Acta 1689:91–102

    Article  Google Scholar 

  21. Sun Y, Oberley LW, Li YA (1988) simple method for clinical assay of superoxide dismutase. Clin Chem 34:497–500

    Article  CAS  Google Scholar 

  22. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2 (-Delta Delta C (T)) method. Methods 25:402–408

    Article  CAS  Google Scholar 

  23. Ji M, Cai S (2005) Nursing of bronchial asthma in children. J Nur Sci 20:68–70

    CAS  Google Scholar 

  24. Ren YF, Li H, Xing XH, Guan HS, Zhang BA, Chen CL, Zhang JH (2015) Preliminary study on pathogenesis of bronchial asthma in children. Ped Res 77:4

    Article  Google Scholar 

  25. Aksoy F, Demirhan H, Veyseller B, Yıldırım YS, Özturan O, Basınoğlu F (2009) Advanced oxidation protein products as an oxidative stress marker in allergic rhinitis. Kulak Burun Bogaz Ihtis Derg 19:279–284

    PubMed  Google Scholar 

  26. Suzy AA, Ricci KS, Arroliga M, Lara AR, Dweik RA (2005) Correlation of systemic superoxide dismutase deficiency to airflow obstruction in asthma. Am J Respir Crit Care Med 172:306–313

    Article  Google Scholar 

  27. Fabian E, Pölöskey P, Kósa L, Elmadfa I, Réthy LA (2011) Activities of antioxidant enzymes in relation to oxidative and nitrosative challenges in childhood asthma. J Asthma 48:351–357

    Article  CAS  Google Scholar 

  28. Katsoulis K, Kontakiotis T, Gerou S, Kougioulis M, Lithoxopoulou H, Papakosta D (2010) Alterations of erythrocyte superoxide dismutase activity in patients suffering from asthma attacks. Arch Chest Dis 73:99–104

    CAS  Google Scholar 

  29. Hung CH, Lin YC, Tsai YG, Lin Y, Kuo C, Tsai M, Kuo C, Liao W (2021) Acrylamide induces mitophagy and alters macrophage phenotype via reactive oxygen species generation. Int J Mol Sci 22:1683

    Article  CAS  Google Scholar 

  30. Rakhee K, Ramakrishnan D, Bajbouj K, Hachim MY, Andrea K et al (2020) Enhanced mitophagy in bronchial fibroblasts from severe asthmatic patients. PLoS ONE 15:1–20

    Google Scholar 

  31. Giuliani C, Napolitano G, Bucci I, Montani V, Monaco F (2001) Nf-kB transcription factor: role in the pathogenesis of inflammatory, autoimmune, and neoplastic diseases and therapy implications. Clin Ter 152:249–253

    CAS  PubMed  Google Scholar 

  32. Cao SS, Luo KL, Shi L (2016) Endoplasmic reticulum stress interacts with inflammation in human diseases. J. Cell. Physiol. 231:288–294

    Article  CAS  Google Scholar 

  33. Wanga X, Yanga X, Lic Y, Wanga X, Zhangd Y et al (2017) Lyn kinase represses mucus hypersecretion by regulating IL-13-inducedendoplasmic reticulum stress in asthma. EBio Med 15:137–149

    Google Scholar 

  34. Lee KS, Jeong JS, Kim SR, Cho SH, Kolliputi N et al (2015) Phosphoinositide 3-kinase-δ regulates fungus-induced allergic lung inflammation through endoplasmic reticulum stress. Thorax 71:52–63

    Article  Google Scholar 

  35. Jain V, Raina S, Gheware AP, Singh R, Rehman R et al (2018) Reduction in polyamine catabolism leads to spermine-mediated airway epithelial injury and induces asthma features. Allergy 73:2033–2045

    Article  CAS  Google Scholar 

  36. North ML, Grasemann H, Khanna N, Inman MD, Gauvreau GM, Scott JA (2013) Increased Ornithine-Derived Polyamines Cause Airway Hyperresponsiveness in a Mouse Model of Asthma. Am J Respir Cell Mol Biol 48:694–702

    Article  CAS  Google Scholar 

  37. Zaleokt S, Alexandrova N, Berdynskykh N, Ignatenko N, Gogol S et al (2004) Role of polyamine in the function of nuclear transcription factor NF-kβ in breast cancer cell. Exp Oncol 26:221–225

    Google Scholar 

  38. Ding L (2019) Downregulation of miR-19b in pediatric asthma is associated with the activation of nuclear factor-kappa B signaling pathway. Int J Clin Exp Med 12:10101–10108

    CAS  Google Scholar 

  39. Escotte S, Tabary O, Dusser D, Majer-Teboul C, Puchelle E, Jacquot J (2003) Fluticasone reduces IL-6 and IL-8 production of cystic fibrosis bronchial epithelial cells via IKK-β kinase pathway. Eur Res J 21:574–581

    Article  CAS  Google Scholar 

Download references

Funding

This research work is performed by using the author's personal fund i.e. the research work is funded by the authors themselves.

Author information

Authors and Affiliations

Authors

Contributions

A. K. Eltokhy, designed the study and did the experimental work. O. Toema, examined the children and classify the groups. O. S. Eldeeb, collected the data and recorded the results. All the team shared in the writing and revision of the article.

Corresponding author

Correspondence to Amira Kamel Eltokhy.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Before being enrolled in the current study, all subjects` parents gave a written informed consents for participation and publication. The study plan was approved by the Local Research Ethics Committee of the Faculty of Medicine, Tanta University (Approval Code 33884/6/20), and was in accordance with the principles of the Declaration of Helsinki II.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Eltokhy, A.K., Toema, O. & El-Deeb, O.S. The Correlation Between PINK-1/Parkin Mediated Mitophagy, Endoplasmic Reticulum Stress and Total Polyamines in Pediatric Bronchial Asthma: An Integrated Network of Pathways. Mol Biol Rep 49, 227–235 (2022). https://doi.org/10.1007/s11033-021-06861-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-021-06861-5

Keywords

Navigation