Induction of procollagen type I gene expression and synthesis in human hepatic stellate cells by 4-hydroxy-2,3-nonenal and other 4-hydroxy-2,3-alkenals is related to their molecular structure.
4-Hydroxy-2,3-nonenal (HNE) has been shown to induce procollagen type I gene expression and synthesis in hepatic stellate cells (HSC), i.e. the cells responsible for deposition of collagen and other extracellular matrix proteins in fibrotic liver. Here we report that the stimulatory effect of HNE mostly depends on the contemporary presence of the hydroxyl group in position C4 and of the double bond between position C2 and C3 since equimolar concentrations of 2,3-nonenal as well as of nonenal did not procollagen type I synthesis either at mRNA or at protein levels. Accordingly to this concept, all the other 4-hydroxy-2,3-alkenals of different chain length tested on cultured human HSC (4-hydroxy-2,3-hexenal, 4-hydroxy-2,3-octenal and 4-hydroxy-2,3-undecenal) strongly induced procollagen type I gene expression and synthesis. The stimulatory effect of 4-hydroxy-2,3-alkenals may depend on the well known ability of these aldehydes to react with either SH-groups or NH2-groups of functional proteins.
Parola
M
M
Dip. Medicina ed Oncologia Sperimentale, Universitià di Torino, Italy.
Pinzani
M
M
Casini
A
A
Leonarduzzi
G
G
Marra
F
F
Caligiuri
A
A
Ceni
E
E
Biondi
P
P
Poli
G
G
Dianzani
M U
MU
D000447:Aldehydes / Q000494:pharmacology*; D000475:Alkenes / Q000494:pharmacology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011347:Procollagen / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects
D000447:Aldehydes; D000475:Alkenes; D011347:Procollagen; D012333:RNA, Messenger; C027576:4-hydroxy-2-nonenal