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 proteins synthesis was evaluated in HeLa cells. Only (E)-4-hydroxyalk-2-enals were active both in racemic and homochiral form. Between the reported primary metabolic products of (E)-4-hydroxynon-2-enal, only the glutathione conjugates were active, whereas (E)-4-hydroxynon-2-enoic acid 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-hydroxynon-2-enal was inactive. Thus, it was established that the active aldehydic 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 binding to proteins could be the first step of the mechanism by which these compounds exert their biological activity.
Allevi
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P
Dipartimento di Chimica e Biochimica Medica, Università degli Studi di Milano, Italia.
Anastasia
M
M
Cajone
F
F
Ciuffreda
P
P
Sanvito
A M
AM
D000447:Aldehydes / Q000737:chemistry* / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D015227:Lipid Peroxidation; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014157:Transcription Factors
D000447:Aldehydes; D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D014157:Transcription Factors; D004247:DNA; D005978:Glutathione; C027576:4-hydroxy-2-nonenal