Cut-off phenomenon in the protective effect of alcohols against lysophosphatidylcholine-induced calcium overload

Abstract

We studied the effect of chain length on the protective effect of alcohols against lysophosphatidylcholine (LPC)-induced Ca2+ overload in neonatal rat cardiomyocytes. We previously found that ethanol retards Ca2+ elevation. Cells were loaded with the Ca2+-sensitive fluorophore fura-2, and changes in fluorescence were followed. The addition of 10 microM LPC increased Ca2+, which reached a plateau after an 8-10 min delay. The presence of 88 mM n-propanol, n-butanol, tert-butanol, or 2,2-dimethylpropanol significantly increased the delay by 94-213%. However, n-pentanol at 2 mM or 88 mM had no protective effect. Among n-alcohols, the increase in lag time was inversely proportional to the length of the carbon chain. Chain length, rather than molecular weight determines the effect, because 2,2-dimethylpropanol had a protective effect. The influence of alcohols on LPC micelle formation was estimated from the increase in octadecyl rhodamine B fluorescence; the increase by n-alcohols was directly proportional to chain length, indicating that micelle formation was not involved in the extension of lag time. The absence of the protective effect when the alcohol aliphatic chain exceeds four carbons suggests that the effect of ethanol may be mediated via a small lipophilic pocket on a protein, or to lateral pressure perturbation in the membrane.

ELISA assays and alcohol: increasing carbon chain length can interfere with detection of cytokines

“…Bordeleau et al (Bordeleau et al, 2005) studied the ability of different alcohols to prevent lysophosphatidylcholine (LPC)-induced Ca 2+ overload in rat cardiomyocytes, loaded with a calcium sensitive fluorophore. They tested the straight chain alcohols ethanol, n-propanol, n-butanol, and n-pentanol as well as some branched chain alcohols at 88 mM.…”

“…Biological effects of other lower straight and branched chain alcohols had been tested on cell cultures (Bordeleau et al, 2005) and laboratory animals (Feller and Crabbe, 1991). In a study by Song et al, the effects of methanol, ethanol, 1-propanol, and n-butanol on TNF-α secretion were tested in an epithelial cell line by ELISA and other methods.…”

Ischemic, genetic and pharmacological origins of cardiac arrhythmias: The contribution of the Quebec Heart Institute

“…When we studied the effect of different alcohols, we found that the increase in critical micellar concentration of LPC by n-alcohols was proportional to chain length (83). However, as the alcohol chain length increased, the protection against LPC-induced Ca 2+ overload decreased and disappeared completely with n-pentanol, implying that micelle formation was not involved in the extension of the lag time.…”