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S-nitrosothiols signaling in cystic fibrosis airways

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Abstract

S-nitrosothiols (SNOs) are small naturally occurring thiol and nitric oxide adducts that participate in many cell signaling pathways in living organisms. SNOs receive widespread attention in cell biology, biochemistry and chemistry because they can donate nitric oxide and/or nitrosonium ions in S-nitrosylation reactions, which are comparable to phosphorylation, acetylation, glutathionylation, and palmitoylation reactions. SNOs have advantageous effects in respiratory diseases and other systems in the body. S-nitrosylation signaling is a metabolically regulated physiological process that leads to specific post-translational protein modifications. S-nitrosylation signaling is faulty in cystic fibrosis (CF) and many other lung diseases. CF is an inherited, lethal autosomal recessive multisystem disease resulting from mutations in the gene encoding the CF transmembrane conductance regulatory (CFTR) protein. F508del CFTR is the most common mutation associated with CF, which results in CFTR misfolding because a phenylalanine is deleted from the primary structure of CFTR. The majority of wild-type CFTR and almost all F508del is degraded before reaching the cell surface. Ultimately, CF researchers have been looking to correct the mutated CFTR protein in the CF patients. Remarkably, researchers have found that SNOs levels are low in the CF lower airway compared to non-CF patients. We have been interested in determining whether SNOs increase CFTR maturation through S-nitrosylation. Maturation of both wild type and mutant F508del CFTR increases SNOs, which up-regulate CFTR maturation. In this review, we summarized our current knowledge of S-nitrosothiols signaling in cystic fibrosis airways.

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Acknowledgements

This research was supported by the Cystic Fibrosis Foundation (Zaman 04GO) and National Institute of Health (1POHL101871-01).

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Authors and Affiliations

  1. Department of Pediatrics and Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA

    Max Liu, Victoria Sawczak & Khalequz Zaman

  2. Department of Material Science Engineering School of Engineering and Keck Center for Cellular Imaging (AP), University of Virginia, Charlottesville, VA, 22908, USA

    Rahim Zaman & Ammasi Periasamy

  3. Department of Physiology, Wayne State University School of Medicine, Detroit, MI, 48201, USA

    Fei Sun

Authors
  1. Max Liu
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  2. Rahim Zaman
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  3. Victoria Sawczak
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  4. Ammasi Periasamy
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  5. Fei Sun
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  6. Khalequz Zaman
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Correspondence to Max Liu or Khalequz Zaman.

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Corresponding editor: BJ RAO.

Corresponding editor: BJ Rao

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Liu, M., Zaman, R., Sawczak, V. et al. S-nitrosothiols signaling in cystic fibrosis airways. J Biosci 46, 111 (2021). https://doi.org/10.1007/s12038-021-00223-w

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