Carbon Nanotube Biodegradation by Neutrophil Myeloperoxidase PI: Valerian E. Kagan, PhD, DSc Widespread applications of engineered nanomaterials, particularly carbon nanotubes (CNT), in different spheres of industry, consumer products, and medicine raise concerns about their possible adverse effects on human health in occupational settings and in the environment.The unique physico-chemical characteristics combined with the vast surface area make the biological effects of CNT largely unpredictable. Our in vivo studies have demonstrated robust and unusual pulmonary inflammatory/oxidative stress responses to single walled CNT (SWCNT) upon exposure of mice via aspiration or inhalation. To date, no demonstration of biodegradation of carbon nanotubes in a physiologically relevant setting has been provided. Our Preliminary results demonstrate that strong oxidants such as hypochlorous acid and oxoferryl species generated as reactive products of the myeloperoxidase reaction may be effective in biodegrading SWCNT. Therefore, we hypothesized that myeloperoxidase in neutrophils has the ability to catalyze the biodegradation of SWCNT and inactivate them inducers of inflammatory responses. To determine the extent to which enzymatic catalysis by human neutrophil myeloperoxidase (hMPO) represents a novel route of biodegradation of SWCNT, we designed experiments formulated in three Specific Aims of the proposal as follows:
Specific Aim 1 will determine molecular mechanisms, products and reaction pathways through which hMPO catalyzes biodegradation of SWCNT.
Specific Aim 2 will define the conditions maximizing biodegradation of SWCNT in human neutrophils and determine possible contribution and role of neutrophil interacions with macrophages in the biodegradation process through the formation of redox phagocytic synapse.
Specific Aim 3 will elucidate hMPO-catalyzed biodegradation of single-walled carbon nanotubes by neutrophils in vivo and quantitatively assess the contribution of the biodegradation process in mitigation of the SWCNT induced inflammatory responses in mouse lung. Discovery of a novel enzymatic pathway for "green" biochemical biodegradation of carbon nanotubes may revolutionize the ways to regulate their distribution in the body and contribute to a roadmap to new effective approaches to decrease their toxicity.

Public Health Relevance

Carbon Nanotube Biodegradation by Neutrophil Myeloperoxidase PI: Valerian E. Kagan, PhD, DSc Widespread applications of engineered nanomaterials, particularly carbon nanotubes (CNT), in different spheres of industry, consumer products, and medicine raise concerns about their possible adverse effects on human health in occupational settings and in the environment. Based on known robust and unusual pulmonary pro-inflammatory effects of CNT, identification of their biodegradation pathways becomes a necessity. We demonstrate that an enzyme of neutrophils - myeloperoxidase - has the ability to catalyze biodegradation of SWCNT and inactivate them as inducers of pulmonary inflammation thus indicating new ways to regulate their distribution in the body and reduce the toxicity.

Agency
National Institute of Health (NIH)
Institute
National Institute for Occupational Safety and Health (NIOSH)
Type
Research Project (R01)
Project #
5R01OH008282-07
Application #
8298043
Study Section
Safety and Occupational Health Study Section (SOH)
Program Officer
Potula, Viji
Project Start
2005-07-01
Project End
2015-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
7
Fiscal Year
2012
Total Cost
$351,957
Indirect Cost
$115,563
Name
University of Pittsburgh
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Kagan, Valerian E; Kapralov, Alexandr A; St Croix, Claudette M et al. (2014) Lung macrophages "digest" carbon nanotubes using a superoxide/peroxynitrite oxidative pathway. ACS Nano 8:5610-21
Kagan, Valerian E; Chu, Charleen T; Tyurina, Yulia Y et al. (2014) Cardiolipin asymmetry, oxidation and signaling. Chem Phys Lipids 179:64-9
Amoscato, A A; Sparvero, L J; He, R R et al. (2014) Imaging mass spectrometry of diversified cardiolipin molecular species in the brain. Anal Chem 86:6587-95
Shvedova, A A; Kisin, E R; Murray, A R et al. (2014) ESR evidence for in vivo formation of free radicals in tissue of mice exposed to single-walled carbon nanotubes. Free Radic Biol Med 73:154-65
Jiang, Jianfei; Bakan, Ahmet; Kapralov, Alexandr A et al. (2014) Designing inhibitors of cytochrome c/cardiolipin peroxidase complexes: mitochondria-targeted imidazole-substituted fatty acids. Free Radic Biol Med 71:221-30
Stoyanovsky, D A; Sparvero, L J; Amoscato, A A et al. (2014) Improved spatial resolution of matrix-assisted laser desorption/ionization imaging of lipids in the brain by alkylated derivatives of 2,5-dihydroxybenzoic acid. Rapid Commun Mass Spectrom 28:403-12
Tyurina, Yulia Y; Domingues, Rosario M; Tyurin, Vladimir A et al. (2014) Characterization of cardiolipins and their oxidation products by LC-MS analysis. Chem Phys Lipids 179:3-10
Chu, Charleen T; Bayýýr, Hulya; Kagan, Valerian E (2014) LC3 binds externalized cardiolipin on injured mitochondria to signal mitophagy in neurons: implications for Parkinson disease. Autophagy 10:376-8
Tyurina, Yulia Y; Poloyac, Samuel M; Tyurin, Vladimir A et al. (2014) A mitochondrial pathway for biosynthesis of lipid mediators. Nat Chem 6:542-52
Shvedova, Anna A; Yanamala, Naveena; Kisin, Elena R et al. (2014) Long-term effects of carbon containing engineered nanomaterials and asbestos in the lung: one year postexposure comparisons. Am J Physiol Lung Cell Mol Physiol 306:L170-82

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