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

Monica Rinaldi, Giuseppina Barrera, Angelo Aquino, Paola Spinsanti, Stefania Pizzimenti, Maria Giulia Farace, Mario Umberto Dianzani, Vito Michele Fazio

Research output: Contribution to journalArticlepeer-review


4-Hydroxynonenal (HNE) is a highly reactive aldehyde, produced by cellular lipid peroxidation, able to inhibit proliferation and to induce differentiation in MEL cells at concentrations similar to those detected in several normal tissues. Inducer-mediated differentiation of murine erythroleukemia (MEL) cells is a multiple step process characterized by modulation of several genes as well as by a transient increase in the amount of membrane-associated protein kinase C (PRC) activity. Here we demonstrate that a rapid translocation of PKC activity from cytosol to the membranes occurs during the differentiation induced by HNE. When PKC is completely translocated by phorbol-12-myristate-13-acetate (TPA), the degree of HNE-induced MEL cells differentiation is highly decreased. However, if TPA is washed out from the culture 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 HNE-induced differentiation in MEL cells. In conclusion, our results demonstrate that HNE-induced MEL cell differentiation is preceded by a rapid translocation of PKC activity, and that the inhibition of this phenomenon prevents the onset of terminal differentiation. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)75-80
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number1
Publication statusPublished - May 27 2000

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology


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