4-hydroxynonenal-induced MEL cell differentiation involves PKC activity translocation

4-Hydroxynonenal (HNE) is a highly reactive aldehyde, produced by cellular lipid peroxidation, able to inhibit proliferation and to induce differentia tion in MEL cells at concentrations similar to those detected in several no rmal tissues. Inducer-mediated differentiation of murine erythroleukemia (M EL) cells is a multiple step process characterized by modulation of several genes as well as by a transient increase in the amount of membrane-associa ted protein kinase C (PKC) activity. Here we demonstrate that a rapid trans location of PKC activity from cytosol to the membranes occurs during the di fferentiation induced by HNE. When PKC is completely translocated by phorbo l-12-myristate-13-acetate (TPA), the degree of HNE-induced MEL cells differ entiation is highly decreased. However, if TPA is washed out from the cultu re medium before the exposition to the aldehyde, HNE gradually resumes its differentiative ability. The incubation of cells with a selective inhibitor of PKC activity, bisindolylmaleimide GF 109203X, partially prevents the HN E-induced differentiation in MEL cells. In conclusion, our results demonstr ate that HNE-induced MEL cell differentiation is preceded by a rapid transl ocation of PKC activity, and that the inhibition of this phenomenon prevent s the onset of terminal differentiation. (C) 2000 Academic Press.