Lipoproteins in hypoxic tumor cells as traps of free radicals

Abstract

We examined the role of main cell protective mechanisms in retaining the high resistance of ascitic cells (EAC, ZAH) to lipid peroxidation with respect to different stages of tumor-organism metabolic interactions. The following mechanisms were studied: (1) the activity of main EAC enzymatic antioxidants (GSH-Px, SOD); (2) changes in lipid metabolism, especially the content of the main PUFA (linoleic and arachidonic fatty acids) in EAC cells; (3) comparison of intracellular resistance between EAC/ZAH cytoplasmic sections (containing LP-granules or not) to lipid peroxidation (initialized directly by UV-light). We found that the high resistance to lipid peroxidation was typical for cytoplasma sections (without LP-granules) on all stages of tumor development in vivo. The intracellular LP-granules become the main sensitive targets for FR-action, but only in the chronic hypoxia state of EAC/ZAH tumor cells. The latter effect developed in close correlation with the following metabolic interactions: (1) increasing the proportion of PUFA (especially, arachidonic and linoleic acids) transported to EAC tumor cells from host organs and accumulated mainly in tumor LP-granules, and (2) decreasing the alpha-tocopherol content of these hypoxic EAC cells while no activation of the main cell antioxidative enzymes (GSH-Px, SOD) took place. The vitality and high resistance of EAC stationary cells were accompanied by the 'paradoxical' state with great differences between the resistance of the intracellular PUFA-rich granules and other cytoplasmic sections. A similar state was found in stationary ZAH cells. The cell state is in good agreement with the Dormandy's suggestion that PUFA-rich granules can trap reactive radical species preventing their interaction with 'critical' PUFA-membranes.

On the Origin of Heterogeneity of Lipofuscin Fluorophores and Their Possible Interrelations

“…(Fig.l). Earlier we have shown that these granules can act as traps for free radicals (19) and can protect whole stationary EAC cells against lethal oxidative injury by this pathway. These distinctions between normal and tumor cell resistance to oxidative stress Under conditions in which free radical actions in low energy cells are being continued, some cell proteins become modified by cross-linking.…”

“…We have previously developed a method (7) for determination of the resistance of living cells and their intracellular compartments to oxidative stress that was induced through the action of UV-light (=365nm). All details of this method were presented in a series of our previous articles (7,8,13,19,20), together with a description of the measurement of spectrokinetic parameters in corresponding fluorescence spectra from single cells.…”

The Principle and the Potential Approach to ROS-dependent Cytotoxicity by Non-pharmaceutical Therapies: Optimal Use of Medical Gases with Antioxidant Properties

“…When UV is irradiated to lipid molecules, hydrogen molecule in double bond in LH (unsaturated fatty acids) is cut off and L• (lipid radical) is formed. When O 2 molecules are exist nearby, L• will be LOO•, which will make peroxide radicals (LOOH), activating membrane enzymes such as PLC and PLA2 [45][46][47][48].…”