Inhibition of D1, D2, and A-cyclin expression in HL-60 cells by the lipid peroxydation product 4-hydroxynonenal.
4-Hydroxynonenal (HNE), a product of lipid peroxidation, is an highly reactive aldehyde that, at concentration similar to those found in normal cells, blocks proliferation and induces a granulocytic-like differentiation in HL-60 cells. These effects are accompained by a marked increase in the proportion G0/G1 cells. The mechanisms of HNE action were investigated by analyzing the expression of the cyclins and cyclin-dependent protein kinases (CDKs), controlling the cell cycle progression. Data obtained by exposing cells to dimethyl sulfoxide (DMSO) were used for comparison. 4-Hydroxynonenal downregulated both mRNA and protein contents of cyclins D1, D2, and A until 24 h from the treatments, whereas DMSO inhibited cyclin D1 and D2 expression until the end of experiment (2 days) and induces an increase of cyclin A until 1 day. Cyclins B and E, and protein kinase CDK2 and CDK4 expressions were not affected by HNE, whereas DMSO induced an increase of cyclin E, B, and CDK2 from 8 h to 1 day. These data are in agreement with previous results indicating a different time-course of accumulation in G0/G1 phases of cells treated with HNE and DMSO and suggest that the HNE inhibitory effect on proliferation and cell cycle progression may depend by the downregulation of D1, D2, and A cyclin expression.
Dipartimento di Medicina e Oncologia Sperimentale, Università di Torino, Italy. pizzimen@medfarm.unito.it
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Pizzimenti
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Barrera
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Dianzani
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Brüsselbach
D000447:Aldehydes / Q000494:pharmacology*; D015153:Blotting, Western; D019925:Cyclin A / Q000096:biosynthesis; D019938:Cyclin D1 / Q000096:biosynthesis; D056742:Cyclin D2; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis*; D016213:Cyclins / Q000096:biosynthesis*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology*
D000447:Aldehydes; C080336:CCND2 protein, human; D019925:Cyclin A; D056742:Cyclin D2; D016213:Cyclins; D019938:Cyclin D1; D018844:Cyclin-Dependent Kinases; C027576:4-hydroxy-2-nonenal; D004121:Dimethyl Sulfoxide