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. 2022 Jan;49(1):227-235. doi: 10.1007/s11033-021-06861-5. Epub 2021 Oct 29.

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.

Keywords: AOPP; Bronchial asthma; IRE1α; NF-κB; Pink/Parkin; Total polyamines.

MeSH terms

  • Asthma / genetics*
  • Asthma / metabolism
  • Case-Control Studies
  • Child
  • Disease Progression
  • Endoplasmic Reticulum Stress
  • Endoribonucleases / metabolism
  • Female
  • Humans
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Male
  • Mitophagy
  • NF-kappa B
  • Polyamines / metabolism*
  • Protein Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • Signal Transduction
  • Ubiquitin-Protein Ligases / genetics*
  • Up-Regulation*

Substances

  • CXCL8 protein, human
  • IL6 protein, human
  • Interleukin-6
  • Interleukin-8
  • NF-kappa B
  • Polyamines
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Protein Kinases
  • ERN1 protein, human
  • PTEN-induced putative kinase
  • Protein Serine-Threonine Kinases
  • Endoribonucleases