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In vivo skin leptin modulation after 14 MeV neutron irradiation: a molecular and FT-IR spectroscopic study

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Abstract

This paper discusses gene expression changes in the skin of mice treated by monoenergetic 14 MeV neutron irradiation and the possibility of monitoring the resultant lipid depletion (cross-validated by functional genomic analysis) as a marker of radiation exposure by high-resolution FT-IR (Fourier transform infrared) imaging spectroscopy. The irradiation was performed at the ENEA Frascati Neutron Generator (FNG), which is specifically dedicated to biological samples. FNG is a linear electrostatic accelerator that produces up to 1.0 × 1011 14-MeV neutrons per second via the D-T nuclear reaction. The functional genomic approach was applied to four animals for each experimental condition (unirradiated, 0.2 Gy irradiation, or 1 Gy irradiation) 6 hours or 24 hours after exposure. Coregulation of a subclass of keratin and keratin-associated protein genes that are physically clustered in the mouse genome and functionally related to skin and hair follicle proliferation and differentiation was observed. Most of these genes are transiently upregulated at 6 h after the delivery of the lower dose delivered, and drastically downregulated at 24 h after the delivery of the dose of 1 Gy. In contrast, the gene coding for the leptin protein was consistently upregulated upon irradiation with both doses. Leptin is a key protein that regulates lipid accumulation in tissues, and its absence provokes obesity. The tissue analysis was performed by monitoring the accumulation and the distribution of skin lipids using FT-IR imaging spectroscopy. The overall picture indicates the differential modulation of key genes during epidermis homeostasis that leads to the activation of a self-renewal process at low doses of irradiation.

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Acknowledgments

The authors are indebted to M. Angelone and M. Pillon (ENEA, Frascati, Italy) for support regarding the FNG, and T. Paunesku (Department of Radiation Oncology, Northwestern University, Chicago) for a very helpful scientific review of all of the work done. This work was partly funded by the Italian Space Agency (ASI) (ASI MoMa contract, 2006–2009). EF and VL received postdoctoral scholarships from the ASI.

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Authors and Affiliations

  1. Laboratori Nazionali di Frascati – INFN, Via E. Fermi 40, 00044, Frascati, Rome, Italy

    M. Cestelli Guidi, C. Mirri & A. Marcelli

  2. ENEA, UT BIORAD-RAB, Lungotevere Thaon di Revel, 76, 00196, Rome, Italy

    E. Fratini & R. Amendola

  3. Dip. Biologia e Biotecnologie “Charles Darwin”, Università La Sapienza, Piazzale Aldo Moro 5, 00185, Rome, Italy

    V. Licursi & R. Negri

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  1. M. Cestelli Guidi
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  2. C. Mirri
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  3. E. Fratini
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  4. V. Licursi
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  5. R. Negri
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  6. A. Marcelli
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  7. R. Amendola
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Correspondence to M. Cestelli Guidi.

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Published in the special paper collection Imaging Techniques with Synchrotron Radiation with guest editor Cyril Petibois.

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Cestelli Guidi, M., Mirri, C., Fratini, E. et al. In vivo skin leptin modulation after 14 MeV neutron irradiation: a molecular and FT-IR spectroscopic study. Anal Bioanal Chem 404, 1317–1326 (2012). https://doi.org/10.1007/s00216-012-6018-3

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  • DOI: https://doi.org/10.1007/s00216-012-6018-3

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