| Abstrakt: |
In the central nervous system (CNS), a number of different pathological processes such as necrosis, Parkinson’s and Alzheimer’s diseases are related to disturbance in calcium homeostasis associated with oxidative stress. Here we compare the susceptibility of rat brain plasma membrane Ca2+-ATPase (PMCA) and sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) isoforms to in vitro oxidative stress, and investigate a putative role of trifluoperazine (TFP), an antipsychotic drug that is also a powerful inhibitor of Ca2+-transporter proteins, in protecting these enzymes. It is shown that, in rat brain, PMCA is very sensitive to the damage induced by preincubation with Fe2+-ascorbate, or Fe2+-ascorbate plus H2O2, while SERCA is resistant. Inhibition of PMCA activity promoted by Fe2+/ascorbate medium is fully prevented by the presence of μM concentrations of either butylated hydroxytoluene (BHT) or TFP, but only partially protected, or reversed, by dithiothreitol (DTT), pointing to some protein cysteine(s) as one of the main targets for a lipid peroxidation-dependent damaging mechanism. However, when 0.5–1 mM H2O2 is added together with Fe2+/ascorbate, both BHT and TFP only partially prevent ATPase activity inhibition, and DTT does not confer any protection, suggesting two possible additional mechanisms involving both lipid peroxidation and direct damage to PMCA at amino acid residues other than cysteines. A possible use of μmolar concentrations of TFP as a direct antioxidant protector for PMCA under oxidative stress conditions is discussed. [ABSTRACT FROM AUTHOR] |
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