CHEEC Seed Grants: FY 2009

Effect of Nanoparticle Physicochemical Properties on Lung Surfactant Function
Investigator: J. Fiegel, Division of Pharmaceutics and Department of Chemical and Biochemical Engineering, University of Iowa

Effect of In Utero Exposure to PCB 136 (2,2',3,3',6,6'- Hexachlorobiphenyl) Enantiomers on Neurodevelopmental Outcomes in Adult Offspring
Investigators: I. Kania-Korwel, and HJ Lehmler, Department of Occupational and Environmental Health, University of Iowa

Monitoring Contaminant Impact on Biofilm Adaptation with Raman Spectroscopy
Investigators: T. Peeples and J. Jessop, Chemical & Biochemical Engineering, University of Iowa

Effects of Environmentally Induced Oxidative Stress on Regulator of G Protein Signaling (RGS) Proteins
Investigator: D. Roman, Division of Medicinal & Natural Products Chemistry, University of Iowa

 


Effect of Nanoparticle Physicochemical Properties on Lung Surfactant Function
Investigator: J. Fiegel, Division of Pharmaceutics and Department of Chemical and Biochemical Engineering, University of Iowa
The lung fluid interface plays an important role in stabilizing the lung during physiological processes such as breathing. Inhaled nanomaterials deposited on the lung fluid surfaces can adversely affect the stability and function of the fluid. However, biophysical and biochemical changes to this interface due to the deposition of nanoparticles with varying physicochemical properties have not been systematically studied. This project aims to elucidate the mechanisms by which nanoparticles alter the function of complex lung fluid interfaces through simultaneous surface rheological and tensiometric studies and fluorescence microscopy. We ultimately aim to develop new paradigms to predict loss of surfactant function based on nanoparticle physicochemical properties (size, surface area, surface charge, relative hydrophobicity and composition).

Publications:  Farnoud AM, Fiege J. Interaction of dipalmitoyl phosphatidylcholine monolayers with a particle-laden subphase. J Phys Chem B. 2013; 117:12124-12134

Farnoud AM, Fiege J. Low concentrations of negatively charged sub-micron particles alter the microstructure of DPPC at the air-water interface; Colloids and Surfaces A: Physicochemical and Engineering Aspects. 415 (2102) 320-327

Effect of In Utero Exposure to PCB 136 (2,2',3,3',6,6'- Hexachlorobiphenyl) Enantiomers on Neurodevelopmental Outcomes in Adult Offspring
Investigators: I. Kania-Korwel, and HJ Lehmler, Department of Occupational and Environmental Health, University of Iowa
Polychlorinated biphenyls (PCBs) are a group of industrial chemicals that persist in the environment and cause adverse neurodevelopmental effects (such as altered brain ryanodine binding) in laboratory animals and in humans. Several neurotoxic PCB congeners, such as PCB 136, are chiral and, as we have shown recently, sensitize ryanodine receptors in an enantiospecific manner in vitro. We hypothesize that exposure to PCB 136 during gestation and lactation causes long-term neurodevelopmental effects in an enantiomer specific manner, with (-)-PCB 136 being more potent and efficacious than (+)-PCB 136. This hypothesis will be tested by investigating enantiomer specific differences (1) in the profile of PCB 136 and its metabolites and (2) brain ryanodine binding in mice exposed during gestation and lactation to (+)- and (-)-PCB 136.

Publications:  Kania-Korwel I, El-Komy MHME, Veng-Pedersen P, Lehmler HJ. Clearance of polychlorinated biphenyl atropisomers is enantioselective in female C57Bl/6 mice. Environ Sci Technol. 2010; 44:2828-2835.

Kania-Korwel I, Duffel MW, Lehmler HJ. Gas chromatographic analysis with chiral cyclodextrin phases reveals the enantioselective formation of hydroxylated polychlorinated biphenyls by rat liver microsomes. Environ Sci Technol. 2011 45:9590-9596.

Kania-Korwel I, Barnhart CD, Stamou M, Truong KM, El-Komy MHME, Lein PJ, Veng-Pedersen P, Lehmler HJ. 2,2',3,5',6-pentachlorobiphenyl (PCB95) and its hydroxylated metabolites are enantiomerically enriched in female mice. Environ Sci Technol. 2012; 46:11393-11401.

Kania-Korwel I, Lehmler HJ. Assigning atropisomer elution orders using atropisomerically enriched polychlorinated biphenyl fractions generated by microsomal metabolism. J Chromat A. 2012;1278:133-144.

Kania-Korwel I, Barnhart CD, Lein PJ, Lehmler HJ. Effect of pregnancy on the disposition of 2,2',3,5',6-pentachlorobiphenyl (PCB 95) atropisomers and their hydroxylated metabolites in female mice. Chem Res Toxicol. 2015; 28:1774-1783.

Monitoring Contaminant Impact on Biofilm Adaptation with Raman Spectroscopy
Investigators: T. Peeples and J. Jessop, Department of Chemical & Biochemical Engineering, University of Iowa
The integration of biofilm flow devices with Raman scattering for bioanalysis and separation is a promising avenue to provide further information regarding complex mixtures of microbes and their adaptive mechanisms that facilitate contaminant biodegradation. To address the acquisition and induction of biotransformation activity, the first hypothesis is that Raman scattering can be used to identify and quantify members of biofilm communities. The second hypothesis is that biofilm formation leads to enhanced levels of atrazine degradation. The formation of biofilm can be evaluated using fluorescence and Raman techniques. Raman scattering can be used to evaluate the persistence of the model contaminant atrazine and metabolites in the flow systems. We expect to advance our mechanistic knowledge of induction in atrazine-mineralizing bacteria adapting to atrazine as a growth substrate. This project is therefore significant because improved bioremediation technologies will lead to reduced environmental contamination and reduce the associated risk to human health.

Publication:  Henry VA, Jessop JL, Peeples TL. Differentiating Pseudomonas sp. strain ADP cells in suspensions and biofilms using Ramen spectroscopy and scanning electron microscopy. Anal Bioanal Chem. 2017; 409:1441-1449.

Effects of Environmentally Induced Oxidative Stress on Regulator of G Protein Signaling (RGS) Proteins
Investigator: D. Roman, Division of Medicinal & Natural Products Chemistry, University of Iowa
Environmental toxins, such as the herbicide paraquat, can cause damage to cells by inducing oxidative stress. 4-hydroxynonenal (4HNE) is the major lipid peroxidation product of oxidative stress and is highly reactive toward protein cysteine residues. RGS4 is a member of the Regulator of G protein signaling (RGS) protein family, and contains a cysteine residue (Cys148) that is sensitive to covalent modification, which irreversibly inhibits its function. RGS proteins are signaling checkpoints downstream of G protein coupled receptor (GPCR) activation and are critical for regulating the magnitude and duration of GPCR-mediated cell signaling events. We hypothesize that this sensitive site on RGS4 (Cys148) is modified during oxidative stress by 4HNE, thus inhibiting RGS4 function. As alterations in GPCR signaling and RGS protein function are evident in neurodegenerative diseases such as Parkinson’s, this proposal seeks to define the role of oxidative stress and 4HNE in RGS4 inhibition and subsequent cellular signaling dysfunction.