STRUCTURAL REQUIREMENTS OF ALDEHYDES PRODUCED IN LPO FOR THE ACTIVATION OF THE HEAT-SHOCK GENES IN HELA-CELLS

The ability of various aldehydes, some of which are produced in lipid peroxidation, to effect heat-shock gene expression and heat-shock prot eins synthesis was evaluated in HeLa cells. Only (E)-4-hydroxyalk-2-en als were active both in racemic and homochiral form. Between the repor ted primary metabolic products of (E)-4-hydroxynon-2-enal, only the gl utathione conjugates were active, whereas (E)-4-hydroxynon-2-enoic aci d and 2-nonen-1,4-diol were inactive. Also, unnatural (E)-5-hydroxynon -2-enal and (E)-5-hydroxyhex-2-enal were active, whereas (E)-6-hydroxy non-2-enal was inactive. Thus, it was established that the active alde hydic compounds must possess an (E)-2 double bond and an hydroxy group in a position suitable for the formation of a cyclic hemiacetal in a possible adduct of these aldehydes with proteins. An irreversible bind ing to proteins could be the first step of the mechanism by which thes e compounds exert their biological activity.