SVIBOR - Project code: 1-03-018

MINISTRY OF SCIENCE AND TECHNOLOGY

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tel.: +385 1 459 44 44, fax: +385 1 459 44 69
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Project code: 1-03-018


EPR ANALYSIS OF THE BIOLOGICALLY DESTRUCTIVE OXIDATION PROCESSES


Main researcher: HERAK, JANKO (15541)


Assistants
Type of research: basic
Duration from: 01/01/91. to 12/31/93.
Papers on project (total): 18
Papers on project quoted in Current Contents: 12
Institution name: Farmaceutsko-biokemijski fakultet, Zagreb (6)
Department/Institute: Division of biophysics
Address: Ante Kovačića 1
City: 10000 - Zagreb, Croatia
Communication
Phone: 385 (0)1 442 182
Fax: 385 (0)1 445 117
Summary: The initial stage of oxidation as a destructive biological process is studied on human plasma lipoproteins exposed to potential sources of initiation of oxidation, and on nucleic caids exposed to ionizing radiation. The former system has been selected because of the potential role of oxidized lipoproteins in the process of atherogenesis, and the latter system because of the inportance of these processes in radiotherapy and radioprotection. For lipoproteins the emphasis is on the processes of spontaneous oxidation (excluding the influence of the surrounding cells ot tissues), on the mechanisms of initiation of oxidation and on the role of antioxidants. For nucleis acids the emphasis is on elucidation of transfer and stabilization of energy deposited by radiation in odered systems of the nucleic-acid bases, and on the role of the radiation-energy traps (protectors). The study is limited mostly to the early events in the process of oxidation, which are characterized by formation of free radicals. Therefore predominantly the EPR spectroscopy is used.

Keywords: lipoproteins, nucleic acids, oxidation, free radicals, ionizing radiation, EPR

Research goals: This study is related to two aspects of oxidative degradation of biologically relevant systems: (a) oxidative modification of natural lipoproteins from human plasma, (b) ionization-induced degradation of nucleic caids. Oxidatively modified lipoproteins, in particular low density lipoprotein (LDL), are metabolized in a different way from that of native lipoproteins. There are special proteins located on the surface of macrophages, which recognize oxidized LDL particles and participate in a receptor-mediated phagocytosis of LDL. It is assumed that a great number of macrophages, rich in lipoproteins, are grouped in so called "foam cells", make an initial phase in a process of atherogenesis. It is a general belief that the oxidation is initiated by the superoxide radicals, O2(-), and that the transition metal ions act as calalizers. However, we show that the initiation of the lipoprotein oxidation, esspecially that of LDL, is a process which also takes place spontaneously, independent of the surroundings of lipoprotein in plasma or tissue. LDL might contain such substances which might intrinsically initiate oxidation. In addition, we prove that oxidation and other chemical modifications change the physical properties of LDL, both in the surface protein fraction and in the lipid core. Recently we have proposed that for a long-range transfer of radiation energy in biologically relevant systems a periodic potential is needed. Double-stranded DNA has a quasi-periodic potential, at least in some segments. The question is, what kind of interactions between the subunits is required in order to enable the electron or hole transfer. To answer that question we studied the long-range transfer of energy/charge/spin in some model systems of the elementary units (bases). One of the main goals is to elucidate whether only the stacked bases (i.e. strong interaction between the bases via pi electrons) enable the transfer. We have shown that the organization of the bases like that in various molecular crystals is suitable for the energy transfer of holes, and that thiocytosine is a suitable radiation energy trap.

COOPERATION - PROJECTS


  1. Name of project: KRO-BIO 2 (GKSS) Transfer of Radiation Energy
    Name of institution: Institut fur Biophysik, Fakultat der Medizin, Universitat des Saarlandes Homburg/Saar Germany
    City: 66454 - Homburg/Saar, Njemačka

COOPERATION - INSTITUTIONS


  1. Name of institution: Institut fuer Biophysik, Universitat des Saarlandes
    Type of institution: University/Faculty
    City: 66454 - Homburg/Saar, Njemačka
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