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.

4-hydroxynonenal and cell cycle

BARRERA, Giuseppina;PIZZIMENTI, Stefania;BRIATORE, FEDERICA;DIANZANI, Mario Umberto
2005

Abstract

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.
24
151
157
BARRERA G; PIZZIMENTI S; LAURORA S; BRIATORE F; TOALDO C; DIANZANI MU
File in questo prodotto:
File Dimensione Formato  
2005 Biofactors.docx

Accesso riservato

Tipo di file: POSTPRINT (VERSIONE FINALE DELL’AUTORE)
Dimensione 32.82 kB
Formato Microsoft Word XML
32.82 kB Microsoft Word XML   Visualizza/Apri   Richiedi una copia
2005 Biofactors.pdf

Accesso riservato

Tipo di file: PDF EDITORIALE
Dimensione 49.09 kB
Formato Adobe PDF
49.09 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
2005 Biofactors.pdf

Accesso aperto

Tipo di file: POSTPRINT (VERSIONE FINALE DELL’AUTORE)
Dimensione 86.75 kB
Formato Adobe PDF
86.75 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/31370
Citazioni
  • ???jsp.display-item.citation.pmc??? 9
  • Scopus 26
  • ???jsp.display-item.citation.isi??? 27
social impact