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Assessing Amide Proton Transfer (APT) MRI Contrast Origins in 9 L Gliosarcoma in the Rat Brain Using Proteomic Analysis

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Abstract

Purpose

To investigate the biochemical origin of the amide photon transfer (APT)-weighted hyperintensity in brain tumors.

Procedures

Seven 9 L gliosarcoma-bearing rats were imaged at 4.7 T. Tumor and normal brain tissue samples of equal volumes were prepared with a coronal rat brain matrix and a tissue biopsy punch. The total tissue protein and the cytosolic subproteome were extracted from both samples. Protein samples were analyzed using two-dimensional gel electrophoresis, and the proteins with significant abundance changes were identified by mass spectrometry.

Results

There was a significant increase in the cytosolic protein concentration in the tumor, compared to normal brain regions, but the total protein concentrations were comparable. The protein profiles of the tumor and normal brain tissue differed significantly. Six cytosolic proteins, four endoplasmic reticulum proteins, and five secreted proteins were considerably upregulated in the tumor.

Conclusions

Our experiments confirmed an increase in the cytosolic protein concentration in tumors and identified several key proteins that may cause APT-weighted hyperintensity.

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Acknowledgments

The authors thank Drs. Silun Wang and Bachchu Lal for experimental assistance and Ms. Mary McAllister for editorial assistance. This work was supported in part by grants from the National Institutes of Health (R01EB009731, R01CA166171, R01NS083435, R21EB015555, P30CA006973, and HHSN268201000032C).

Conflict of Interest

None of the authors has any conflict of interest.

Author information

Authors and Affiliations

  1. Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Kun Yan, Chen Yang, Kai Zhang, Shanshan Jiang, Dong-Hoon Lee, Hye-Young Heo, Yi Zhang & Jinyuan Zhou

  2. College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, Hubei, China

    Kun Yan

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

    Zongming Fu

  4. Mass Spectrometry and Proteomics Facility, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Robert N. Cole

  5. Bayview Proteomics Center, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Jennifer E. Van Eyk

  6. Advanced Clinical BioSystems Research Institute, Heart Institute, and Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Jennifer E. Van Eyk

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  1. Kun Yan
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  2. Zongming Fu
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  3. Chen Yang
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Correspondence to Jinyuan Zhou.

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Yan, K., Fu, Z., Yang, C. et al. Assessing Amide Proton Transfer (APT) MRI Contrast Origins in 9 L Gliosarcoma in the Rat Brain Using Proteomic Analysis. Mol Imaging Biol 17, 479–487 (2015). https://doi.org/10.1007/s11307-015-0828-6

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