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Parkson Lee-Gau Chong, PhD

Professor, Biochemistry

Telephone:  215-707-4182

Fax:  215-707-7536

Email: pchong02@temple.edu

Department of Biochemistry

Center for Substance Abuse Research

Department of Biochemistry
University of Illinois at Champaign-Urbana
Urbana, Illinois

 

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Project 1: Structure and Function of Thermoacidophilic Archaeal Membranes

The long-term goals of this research are to understand how the Archaea (archaebacteria) live in extreme environments and to use the Archaeal bipolar tetraether lipids for technological applications. The Archaea, including halophiles, methanogens, and extreme thermophiles, are curious and remarkable organisms; and, their lipids are structurally distinctly different from their bacterial and eukaryotic counterparts. The native habitat of the thermoacidophilic archaeon Sulfolobus acidocaldarius, which is the focus of this research, is hot (65-80 oC) and acidic (pH 2-3) sulfur springs. The plasma membrane of S. acidocaldarius not only serves as a barrier between the low pH extracellular environment and the neutral pH intracellular compartment (pH 6.5), but also performs proton pumping and other cellular activities at high temperatures. The ability of the plasma membrane to achieve these goals in extreme environments is not clearly understood, although there is evidence suggesting that it has something to do with its unique bipolar tetraether lipid structures which contain cyclopentane rings, branched methyl groups, ether linkages, and sugar moieties. The objective of this research is to elucidate the physical origin of the remarkable thermal, chemical, and mechanical stability of the archaebacterial plasma membrane via a systematic study on the physical properties of liposomes composed of bipolar tetraether lipids (specifically, polar lipid fraction E, PLFE) isolated from S. acidocaldarius. Fluorescence spectroscopy and microscopy, photon correlation spectroscopy, FT-IR, x-ray scattering, high-pressure technology, electron microscopy, and molecular modeling are the major tools to be used. Temperature, pressure, pH and salt concentrations are the experimental variables. Membrane properties to be investigated include solute permeability, membrane packing, membrane aggregation/fusion, and protein-lipid interactions. These studies will give molecular insights into the structure-function relationship of thermoacidophilic archaeal membranes in extreme environments and may also lead to the development of PLFE liposomes or films for applications in membrane protein crystallization, drug delivery, and the separation, storage, protection, and purification of biomaterials.

Project 2: Regulation of Surface Acting Enzymes by Cholesterol Superlattice

The main goals of this research are to demonstrate a new type of regulation of membrane surface acting enzymes and to establish a new perspective for the functional importance of membrane cholesterol. The hypothesis is that the activities of membrane surface acting enzymes, such as secretory phospholipase A2 (sPLA2) and cholesterol oxidase, can be modulated by cholesterol content in an alternating manner, via changes in the size of regularly distributed lipid membrane areas. According to the newly established sterol regular distribution model, cholesterol can be regularly distributed into superlattices. Regular regions coexist with irregular regions, and the ratio of these two is at a local maximum at critical sterol mole fractions (Cr). In the range of 15-55 mol% cholesterol in diacylphospholipid or sphingomyelin bilayers, the Crs are 15.4, 20.0, 22.2, 25.0, 33.0, 40.0 and 50.0 mol%. Compared to the situations in the irregular regions, membrane packing in the regular regions is tighter, at which sterol is more exposed to the aqueous phase. Based on this theory, the activities of sPLA2 and cholesterol oxidase are expected to exhibit a biphasic change at the Crs, since their activities depend on membrane defects and the substrate accessibility respectively. This hypothesis will be thoroughly tested using a variety of liquid crystalline cholesterol-containing bilayers with varying degrees of compositional complexity. In addition, the underlying molecular mechanism will be investigated in depth. The effects of membrane curvature stress and the degree and position of cis double bonds in the acyl chain on the cholesterol concentration dependencies of the activities of these two enzymes will be examined in the context of sterol superlattice. Fluorescence and absorbance-based enzymic assays, HPLC, high-pressure fluorescence spectroscopy and other biophysical techniques will be employed. The obtained results will unravel a new and important regulatory mechanism for surface acting enzymes. Many surface acting enzymes, such as secretory and cytosolic phospholipase A2, triacylglycerol lipases, phospholipases C & D and protein kinase C, play pivotal roles in signal transduction, venom action, inflammation, digestion of lipids and the biosynthesis of the eicosanoids. The eicosanoids, for example, are potent regulators of platelet activation, thrombus formation and blood vessel dilation, and are of vital importance in eliciting heart diseases and strokes.

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Venegas B, Sugar IP, Chong PL-G.  Critical factors for detection of biphasic changes in membrane properties at specific sterol mole fractions for maximal superlattice formation. J. Phys. Chem. B., in press, 2007.

Chong PL-G, Olsher, M. Fluorometric assay for detection of sterol oxidation in liposomal membranes. In “Membrane Lipid Protocols”, Dopico, A., ed., Humana Press Inc., Totowa, NJ., in press, 2007.

Chong PL-G, Venegas B, OlsheR M. Fluorescence detection of signs of sterol superlattice formation in lipid membranes. In “Membrane Lipid Protocols”, Dopico, A., ed., Humana Press Inc., Totowa, NJ., in press, 2007.

Chong PL-G. Physical properties of membranes composed of tetraether archaeal lipids. In “Thermophiles”, Robb F, ed., CRC Press, FL., in press, 2007.

Chong PL-G, Olsher M.  Fluorescence studies of lipid lateral organization in liposomal membranes (review). Soft Materials, 2:85-105, 2004.

Chong PL-G, Zein M, Khan TK, Winter R.  Structure and conformation of bipolar tetraether lipid membranes derived from thermoacidophilic archaeon sulfolobus acidocaldarius as revealed by small-angle X-ray scattering and high pressure FT-IR spectroscopy. J. Phys. Chem. 107:8694-8700, 2003.

Gliozzi A, Relini A, Chong PL-G.  Structure and permeability properties of biomimetic membranes of bolaform archaeal tetraether lipids (review). J. Membrane Science, 206:131-147, 2002.

Wang MM, Sugar IP, Chong PL-G.  Effect of double bond position on dehydroergosterol fluorescence intensity dips in phosphatidylcholine bilayers with saturated sn-1 and monoenoic sn-2 acyl chains. J. Phys. Chem. 106:6338-6345, 2002.

Sugar IP, Michonova-Alexova E, Chong PL-G.  Geometrical properties of gel and fluid clusters in DMPC/DSPC bilayers: Monte Carlo simulation approach using a two-state model. Biophys. J. 81:2425-2441, 2001.

Zhou JG, Koulas S, Chong PL-G. Shape memory alloy activated high-pressure optical cell for biophysical studies. Rev. Sci. Instrum. 71:4249-4256, 2000.

Bagatolli L, Gratton E, Khan TK, Chong PL-G.  Two-photon fluorescence microscopy studies of bipolar tetraether giant liposomes from thermoacidophilic archaebacteria sulfolobus acidocaldarius. Biophys. J. 79:416-425, 2000.

Zhou JG, Ostrow A, Koulas SH, Chong PL-G. New instrument design of high pressure optical cell for biophysical and chemical research. Rev. Sci. Instrum. 69:3958-3965, 1998.

Chong PL-G. Membrane free volume variation with bulky lipid concentration by regular distribution: A functionally important property explored by pressure studies of phosphatidylcholine bilayers. in “High Pressure Effects in Molecular Biophysics and Enzymology” (eds., Markley JL, Northrop DB, and Royer CA), Oxford Publishing, pp. 298-313, 1996.

Chong PL-G, Liu F, Wang MM, Truong K, Sugar IP, Brown RE. Fluorescence evidence for cholesterol regular distribution in phosphatidylcholine and in sphingomyelin lipids bilayers. J. Fluorescence 6:221-230, 1996.

Sugar IP, Tang D, Chong PL-G. Monte Carlo simulation of lateral distribution of molecules in a two-component lipid membrane. Effect of long-range repulsive interactions. J. Phys. Chem. 98:7201-7210, 1994.

Sugar IP, Zeng J, Vauhkonen M, Somerharju P, Chong PL-G. Use of Fourier transforms in the analysis of fluorescence data. 2. fluorescence of pyrene-labeled phosphatidylcholine in lipid bilayer membranes. Test of the Birks model. J. Phys. Chem. 95:7516-7523, 1991.

Sugar IP, Zeng J, Vauhkonen M, Somerharju P, Chong PL-G. Use of Fourier transforms in the analysis of fluorescence data. 3. fluorescence of pyrene-labeled phosphatidylcholine in lipid bilayer membrane. A three-state model. J. Phys. Chem. 95:7524-7534, 1991.

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Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

19535683. Scott RC, Rosano JM, Ivanov Z, Wang B, Chong PL, Issekutz AC, Crabbe DL, Kiani MF, Targeting VEGF-encapsulated immunoliposomes to MI heart improves vascularity and cardiac function. FASEB J 23:10(3361-7)2009 Oct

19477316. Brown DA, Venegas B, Cooke PH, English V, Chong PL, Bipolar tetraether archaeosomes exhibit unusual stability against autoclaving as studied by dynamic light scattering and electron microscopy. Chem Phys Lipids 159:2(95-103)2009 Jun

19172383. Pattillo CB, Venegas B, Donelson FJ, Del Valle L, Knight LC, Chong PL, Kiani MF, Radiation-guided targeting of combretastatin encapsulated immunoliposomes to mammary tumors. Pharm Res 26:5(1093-100)2009 May

19010302. Chong PL, Zhu W, Venegas B, On the lateral structure of model membranes containing cholesterol. Biochim Biophys Acta 1788:1(2-11)2009 Jan

18694720. Olsher M, Chong PL, Sterol superlattice affects antioxidant potency and can be used to assess adverse effects of antioxidants. Anal Biochem 382:1(1-8)2008 Nov 1

18689464. Venegas B, Wolfson MR, Cooke PH, Chong PL, High vapor pressure perfluorocarbons cause vesicle fusion and changes in membrane packing. Biophys J 95:10(4737-47)2008 Nov 15

17980352. Huang P, Xu W, Yoon SI, Chen C, Chong PL, Unterwald EM, Liu-Chen LY, Agonist treatment did not affect association of mu opioid receptors with lipid rafts and cholesterol reduction had opposite effects on the receptor-mediated signaling in rat brain and CHO cells. Brain Res 1184:(46-56)2007 Dec 12

17980152. Huang P, Chen C, Xu W, Yoon SI, Unterwald EM, Pintar JE, Wang Y, Chong PL, Liu-Chen LY, Brain region-specific N-glycosylation and lipid rafts association of the rat mu opioid receptor. Biochem Biophys Res Commun 365:1(82-8)2008 Jan 4

17951733. Chong PL, Venegas B, Olsher M, Fluorescence detection of signs of sterol superlattice formation in lipid membranes. Methods Mol Biol 400:(159-70)2007

17951732. Chong PL, Olsher M, Fluorometric assay for detection of sterol oxidation in liposomal membranes. Methods Mol Biol 400:(145-58)2007

17441759. Venegas B, Sugár IP, Chong PL, Critical factors for detection of biphasic changes in membrane properties at specific sterol mole fractions for maximal superlattice formation. J Phys Chem B 111:19(5180-92)2007 May 17

17141202. Huang P, Xu W, Yoon SI, Chen C, Chong PL, Liu-Chen LY, Cholesterol reduction by methyl-beta-cyclodextrin attenuates the delta opioid receptor-mediated signaling in neuronal cells but enhances it in non-neuronal cells. Biochem Pharmacol 73:4(534-49)2007 Feb 15

16505160. Xu W, Yoon SI, Huang P, Wang Y, Chen C, Chong PL, Liu-Chen LY, Localization of the kappa opioid receptor in lipid rafts. J Pharmacol Exp Ther 317:3(1295-306)2006 Jun

15980181. Chong PL, Ravindra R, Khurana M, English V, Winter R, Pressure perturbation and differential scanning calorimetric studies of bipolar tetraether liposomes derived from the thermoacidophilic archaeon Sulfolobus acidocaldarius. Biophys J 89:3(1841-9)2005 Sep

15803663. Kanichay R, Boni LT, Cooke PH, Khan TK, Chong PL, Calcium-induced aggregation of archaeal bipolar tetraether liposomes derived from the thermoacidophilic archaeon Sulfolobus acidocaldarius. Archaea 1:3(175-83)2003 Oct

15697233. Olsher M, Yoon SI, Chong PL, Role of sterol superlattice in free radical-induced sterol oxidation in lipid membranes. Biochemistry 44:6(2080-7)2005 Feb 15

14979712. Wang MM, Olsher M, Sugár IP, Chong PL, Cholesterol superlattice modulates the activity of cholesterol oxidase in lipid membranes. Biochemistry 43:8(2159-66)2004 Mar 2

12093540. Chong PL, Sugár IP, Fluorescence studies of lipid regular distribution in membranes. Chem Phys Lipids 116:1-2(153-75)2002 Jun

10823467. Gabriel JL, Chong PL, Molecular modeling of archaebacterial bipolar tetraether lipid membranes. Chem Phys Lipids 105:2(193-200)2000 Apr

10692324. Khan TK, Chong PL, Studies of archaebacterial bipolar tetraether liposomes by perylene fluorescence. Biophys J 78:3(1390-9)2000 Mar

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