Premium
Effects of polyamine imbalance on the induction of stress genes in hepatocarcinoma cells exposed to heat shock
Author(s) -
Desiderio M A,
Tacchini L,
Anzon E,
Pogliaghi G,
Radice L,
BernelliZazzera A
Publication year - 1996
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510240125
Subject(s) - spermidine , putrescine , ornithine decarboxylase , polyamine , spermine , heat shock factor , hsp70 , microbiology and biotechnology , heat shock , biology , heat shock protein , gene expression , biochemistry , chemistry , gene , enzyme
The expression of hsp70–the inducible member of the corresponding heat shock gene family‐of the oxidative stress marker gene heme oxygenase (HOx), and of the immediate early response genes c‐ fos and c‐ jun has been studied in FAO hepatocarcinoma cells depleted of polyamines and exposed to heat shock. Depletion of polyamines was obtained in short‐ term experiments (24‐48 hours) by the use of alpha difluoromethylornithine (DFMO), a classical inhibitor of ornithine decarboxylase (ODC), or of the combination of the newly available inhibitors of ODC and S‐adenosylmethionine decarboxylase, i.e., (2R,5R)‐hept‐6‐yne‐2,5‐diamine (MAP) and 5′[(Z)‐4‐aminobut‐2‐enyl]methylanino‐5‐ deoxyadeno‐si ne (AbeAdo). Under our experimental conditions polyamine imbalance was realized without appreciable growth‐related genes. Decreases of putrescine and spermidine 48 hours after DFMO prevented the induction of hsp70 messenger RNA (mRNA), whereas depletion spermidine and spermine obtained with MAP/AbeAdo decreased intensity and duration of post‐heat shock accumulation of hsp70 mRNA. Inductions of HOx, c‐ jun and c‐ fos were also inhibited. Because MAP/AbeAdo caused also an intracelluar accumulation of putrescine, we tested the effect of exogenous putrescine, which was found to stabilize the mRNAs for hsp70 and c‐ jun . Hsp70 and HOx are thought to play a protective role, and the proteins of c‐ jun and c‐ fos constitute the transcription factor activator protein‐1, which is involved in the transcription of many defensive products. Therefore, the integrity of polyamine pool seems to be a necessary permissive condition for an effective response of the cells to adverse environmental changes.