Calcium- and pH-linked oligomerization of sorcin causing translocation from cytosol to membranes

Sorcin, a cytosolic calcium-binding protein containing a pair of EF-hand motifs, undergoes a Ca2+-dependent translocation to the cell membrane, The underlying conformational change is similar at pH 6.0 and 7.5 and consists in an increase in overall hydrophobicity that involves the aromatic residues and in particular the two tryptophan residues which become less exposed to solvent, The concomitant association from dimers to tetramers indicates that the tryptophan residues, which are located between the EF-hand sites, become buried at the dimer-dimer interface, Ca2+-bound sorcin displays a striking difference in solubility as a function of pH that has been ascribed to the formation of calcium-stabilized aggregates. (C) 1997 Federation of European Biochemical Societies

Dietary alpha-linolenic acid reduces COX-2 expression and induces apoptosis of hepatoma cells.

Fatty acid synthetase (FAS) is overexpressed in various tumor tissues, and its inhibition and/or malonyl-CoA accumulation have been correlated to apoptosis of tumor cells. It is widely recognized that both omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) depress FAS expression in liver, although epidemiological and experimental reports attribute antitumor properties only to omega-3 PUFA. Therefore, we investigated whether lipogenic gene expression in tumor cells is differently regulated by omega-6 and omega-3 PUFAs. Morris hepatoma 3924A cells were implanted subcutaneously in the hind legs of ACI/T rats preconditioned with high-lipid diets enriched with linoleic acid or alpha-linolenic acid. Both-high lipid diets depressed the expression of FAS and acetyl-CoA carboxylase in tumor tissue, this effect correlating with a decrease in the mRNA level of their common sterol regulatory element binding protein-1 transcription factor. Hepatoma cells grown in rats on either diet did not accumulate malonyl-CoA. Apoptosis of hepatoma cells was induced by the alpha-linolenic acid-enriched diet but not by the linoleic acid-enriched diet. Therefore, in this experimental model, apoptosis is apparently independent of the inhibition of fatty acid synthesis and of malonyl-CoA cytotoxicity. Conversely, it was observed that apoptosis induced by the alpha-linolenic acid-enriched diet correlated with a decrease in arachidonate content in hepatoma cells and decreased cyclooxygenase-2 expression