Vol. 41, No. 4, April 1997 BIOCHEMISTRY and MOLECULAR BIOLOGY INTERNATIONAL Pages 647-655 LIPID PEROXIDATION BOTH INHIBITS Ca2+-ATPase AND INCREASES Ca 2+ PERMEABILITY OF ENDOPLASMIC RETICULUM MEMBRANE Peter Radcty, Peter Kaplfin, Viera M&egovd, and Jfin Lehotsk~ Comenius University, Jessenius Faculty of Medicine, Department of Medical Biochemistry, Mald Hora 4, SK-036 O1Martin, Slovak RepubBc ReceivedJanuary2, 1997 SUMMARY. Incubation of reticular membranes with FeZ+-EDTA and H20 z plus Fe>-EDTA at 37 ~ for 30 rain. led to the loss &membrane's efficiency to sequester Ca> to 21.8 % and 3.6 % of control values, respectively. The incubation of microsomes with Fe>-EDTA and H20 z plus Fe>-EDTA also caused decrease of Ca2+-ATPase activity; to 44.9 % and 44.4 % (measured under the same conditions as Ca>-uptake) or to 79.6 % and 62.1% (uncoupled from Ca> transport by detergent). In addition, incubation of membranes with Fe>-EDTA and H20 z plus Fe>-EDTA at 37 ~ for 30 rain. led to the increase of Ca> permeability to 125.1% and 124.2 %, respectively. Preincubation of membranes with membrane-soluble antioxidants (U-74500A, U-83836E, t-butyl hydroxytoluene and stobadine) protected the reticular membranes against depression of Ca> uptake values and Ca>-ATPase inhibition in a dose and an antioxidant nature dependent manner. Our results indicate that both processes, Ca>- ATPase inhibition and increase of endoplasmic reticulum membrane Caz+ permeability, participate in the lipid peroxidation induced loss of membrane's efficiency to sequester Ca2+. Key words: lipid peroxidation; flee radicals; Ca2+-transport; brain. Free radicals and a subsequently initiated lipid peroxidation are often implicated in the pathophysiolgy of various neurodegenerative diseases (1, 2), brain trauma (3) and ischemia- reperfusion injury (4, 5,). They act as possible mediators of cellular injury through nonspecific modification and disruption of proteins, phospholipids and nucleic acids (6). Biological membranes exerting important biological functions are readily susceptible to free radical attack. The deleterious effects of the free radicals on membranes are thought to be due to peroxidation of membrane lipids; this peroxidation may cause the damage to the membrane structure and function (6), including membrane fluidity, ion permeability and modulation of membrane spanning protein activities (7). On the other side, modification of the polypeptide chain by free radicals can not be excluded (8, 9,). Although the plasma membrane is supposed to be a crucial membrane target of flee radical attack, membranes of intracellular organeltes are also very important in this respect (10). In the cells of the central nervous system, endoplasmic reticulum (ER) exerts an 647 1039-9712/97/04064%09505.00/0 Copyright 9 1997 by Academic Press Australia. All rights of reproduction in any.fin'm reserved.