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Characterization of In-Vivo 1H-NMR Biomarkers for Pulmonary Phospholipidosis

EMSL Project ID
17497
Award DOI
https://dx.doi.org/10.46936/cpbl.proj.2006.17497/60002242

Abstract

 The primary goal of this project is to test the potential utility of slow MAS 1H-NMR methods for directly monitoring pulmonary phospholipid accumulation in live animals and in real-time. It is anticipated that the direct biochemical analysis of lung tissue will eliminate the many problems associated with ex vivo sample preparation. This may greatly improve current understanding of the potential health risks associated with its induction by either inhaled materials and/or pharmacological agents.

To carry out the proposed work, mice will be used as test animals, silica dust will be used as model particulate matter (PM), and standard laboratory evaluations on excised lung tissues will be carried out to validate in vivo slow-MAS results. Additionally, standard magnetic resonance imaging of the lungs of mice prior to and after silica exposure will be performed to detect any accompanying inflammation. Work is also proposed using cell cultures from other projects in this focus area in order to more fully integrate research efforts with ongoing activities. For this, more traditional high-resolution NMR techniques will be employed, including the use of (13C, or 15N) isotope enriched substrates to obtain the metabolite profile of cell cultures from related projects. Slow-MAS NMR will also be employed to study dense cell systems or cell aggregates where standard NMR fails. It is expected that a link between the onset pulmonary phospholipidosis in animals and that in cultured cells from in vitro studies will be established by using such an integrated approach. Finally, the noninvasive NMR methods (both slow-MAS NMR and MRI) will be applied to study pulmonary response of live mice exposed to other PMs such as silica coated with lipopolysaccharide (LPS) and biological/zoonotic agents, initially using Yersinia ruckeri, the enteric redmouth disease bacterium found in fish.

Project Details

Project type
Capability Research
Start Date
2006-04-18
End Date
2007-05-21
Status
Closed
Released Data Link
https://search.emsl.pnnl.gov/?project_id_search=17497

Team

Principal Investigator

Jian-zhi Hu
Institution
Pacific Northwest National Laboratory

Team Members

Donald Rommereim
Institution
Environmental Molecular Sciences Laboratory

Kathleen McAteer
Institution
Washington State University Tri-Cities

Kevin Minard
Institution
Pacific Northwest National Laboratory

Robert Wind
Institution
Pacific Northwest National Laboratory

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Application of High-Resolution 1H MAS NMR Spectroscopy to the Analysis of Intact Bones from Mice Exposed to Gamma Radiation Qibin Zhang, Jian Zhi Hu, Donald N. Rommereim, Mark K. Murphy, Richard P. Phipps, David L. Husoc and John F. Dicelloc RADIATION RESEARCH 172, 000–000 (2009) DOI: 10.1667/RR1715.1
Hu JZ. 2011. "Slow Magic Angle Sample Spinning: A Non- or Minimally Invasive Method for High- Resolution 1H Nuclear Magnetic Resonance (NMR) Metabolic Profiling ." Chapter 20 in Metabolic Profiling: Methods and Protocols. Methods in Molecular Biology, vol. 708, ed. TO Metz, pp. 335-364. Humana Press, New York, NY.
Hu JZ, DN Rommereim, KR Minard, A Woodstock, BJ Harrer, RA Wind, RP Phipps, and PJ Sime. 2008. "Metabolomics in Lung Inflammation: A High Resolution ¹H NMR Study of Mice Exposed to Silica Dust ." Toxicology Mechanisms and Methods 18(5):385-398. doi:10.1080/15376510701611032
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Hu JZ, Q Zhang, DN Rommereim, NG Isern, DW Hoyt, TO Metz, MK Murphy, K Mcateer, DL Huso, JF Dicello, and RP Phipps. 2008. "Metabolic Changes in Mice Exposed to High let Iron Ion and Proton Radiation." Abstract submitted to 19th Annual NASA Spacce Radiation Investigators Workshop, Philadelphia, PA. PNWD-SA-8187.
Wang X, MY Hu, M Liu, and JZ Hu. 2014. "Metastatic Melanoma Induced Metabolic Changes in C57BL/6J Mouse Stomach Measured by 1H NMR Spectroscopy." Metabolomics 4(2):, doi:10.4172/2153-0769.1000135