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 react ive 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 propor tion G0/G1 cells. The mechanisms of HNE action were investigated by analyzi ng 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 dow nregulated 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 un til 1 day. Cyclins B and E, and protein kinase CDK2 and CDK4 expressions we re not affected by HNE, whereas DMSO induced an increase of cyclin E, B, an d 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 cell s treated with HNE and DMSO and suggest that the HNE inhibitory effect on p roliferation and cell cycle progression may depend by the downregulation of D1, D2, and A cyclin expression. (C) 1999 Elsevier Science Inc.