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Cell proliferation and oxidative stress pathways are modified in fibroblasts from Sturge–Weber syndrome patients

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Abstract

Sturge–Weber syndrome (SWS) is defined by vascular malformations of the face, eye and brain and an underlying somatic mutation has been hypothesized. We employed isobaric tags for relative and absolute quantification (iTRAQ-8plex)-based liquid chromatography interfaced with tandem mass spectrometry (LC–MS/MS) approach to identify differentially expressed proteins between port-wine-derived and normal skin-derived fibroblasts of four individuals with SWS. Proteins were identified that were significantly up- or down-regulated (i.e., ratios >1.2 or <0.8) in two or three pairs of samples (n = 31/972 quantified proteins) and their associated p values reported. Ingenuity pathway analysis (IPA) tool showed that the up-regulated proteins were associated with pathways that enhance cell proliferation; down-regulated proteins were associated with suppression of cell proliferation. The significant toxicologic list pathway in all four observations was oxidative stress mediated by Nrf2. This proteomics study highlights oxidative stress also consistent with a possible mutation in the RASA1 gene or pathway in SWS.

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Acknowledgments

We acknowledge grant support from Hunter’s Dream for a Cure and assistance obtaining samples from the Sturge–Weber Foundation and the Maryland Brain Bank. We thank Aditya K. Sreenivasan and Kira Lanier for editing this manuscript, and subjects who donated tissue.

Conflict of interest

The authors do not have a financial relationship with Hunter’s Dream for a Cure Foundation.

Author information

Authors and Affiliations

  1. Departments of Neurology and Developmental Medicine, Hugo Moser Kennedy Krieger Research Institute, Baltimore, USA

    Shilpa D. Kadam & Anne M. Comi

  2. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, USA

    Shilpa D. Kadam, Paul A. Watkins & Anne M. Comi

  3. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, USA

    Anne M. Comi

  4. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, USA

    Shilpa D. Kadam

  5. Institute for Basic Biomedical Sciences, Johns Hopkins University School of Medicine, Baltimore, USA

    Marjan Gucek

  6. Institute for Basic Biomedical Sciences, Mass Spectrometry and Proteomics Facility, Johns Hopkins University School of Medicine, Baltimore, USA

    Robert N. Cole

  7. Department of Neurogenetics, Hugo Moser Kennedy Krieger Research Institute, Baltimore, USA

    Paul A. Watkins

Authors
  1. Shilpa D. Kadam
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  2. Marjan Gucek
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  3. Robert N. Cole
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  4. Paul A. Watkins
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  5. Anne M. Comi
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Correspondence to Anne M. Comi.

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Kadam, S.D., Gucek, M., Cole, R.N. et al. Cell proliferation and oxidative stress pathways are modified in fibroblasts from Sturge–Weber syndrome patients. Arch Dermatol Res 304, 229–235 (2012). https://doi.org/10.1007/s00403-012-1210-z

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  • DOI: https://doi.org/10.1007/s00403-012-1210-z

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