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4‐Hydroxynonenal and cell cycle
Author(s) -
Barrera Giuseppina,
Pizzimenti Stefania,
Laurora Stefano,
Briatore Federica,
Toaldo Cristina,
Dianzani Mario Umberto
Publication year - 2005
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.5520240118
Subject(s) - cyclin dependent kinase , cell cycle , retinoblastoma protein , microbiology and biotechnology , 4 hydroxynonenal , cell growth , cyclin dependent kinase 2 , cyclin , e2f , kinase , chemistry , cyclin a , cyclin e , cyclin d1 , biology , cell , lipid peroxidation , biochemistry , oxidative stress
Lipid peroxidation is very low in proliferating cells and tumours and it might have a role in the regulation of cell proliferation and differentiation by acting through its products. 4‐hydroxynonenal (HNE) has been proposed as a mediator of lipoperoxidation effects. It has been demonstrated that HNE can inhibit cell growth and induce differentiation in different leukemic cell lines. The onset of differentiation, induced by HNE, was accompanied by a reduction of c‐myc expression. In HL‐60 cells, HNE induced the accumulation of cells in the G0/G1 phase of the cell cycle. Cell cycle progression is regulated by three protein classes, the cyclins, the cyclin‐dependent kinases (CDKs), and the CDK inhibitors (CKIs). In HL‐60 cells, HNE decreased the expression of cyclin D1, D2 and A and caused an increase of p21 (the most important CKI) expression, whereas it did not affect CDK expressions. Since cyclins D/CDK2 and cyclin A/CDK2 phosphorylate pRB, HNE caused an increase of hypophosphorylated pRb. Hypophosphorylated pRb binds and inactivates the E2F transcription factors. Band‐shift experiments demonstrated that HNE caused a decrease of “free“ E2F, as well as an increase of pRb (and pRB family members) bound to E2F with consequent repression of the transcription.