4.7 Article

Lactoferrin Modulates Induction of Transcription Factor c-Fos in Neuronal Cultures

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MDPI
DOI: 10.3390/ijms24098373

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human lactoferrin; transcription factor c-Fos; neuronal cultures; stimulation; cytoplasmic and nuclear localization

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This study investigates the ability of lactoferrin to regulate gene expression involved in long-term neuroplasticity, and its effect on neuronal processes. The findings show that exogenous lactoferrin can enter the nuclei of neuronal cells and colocalize with the transcription factor c-Fos, leading to increased expression of c-Fos. These results suggest that lactoferrin may function as a modulator of neuronal processes and provide new insights into its regulatory effects on cell function.
Lactoferrin (Lf) is a multifunctional protein from the transferrin family. Of particular interest is the ability of Lf to affect a wide range of neuronal processes by modulating the expression of genes involved in long-term neuroplasticity. The expression of the immediate early gene c-fos that is rapidly activated in response to external influences, and its product, transcription factor c-Fos, is widely used as a marker of long-term neuronal plasticity. The present study aims to examine the effect of human Lf on the induction of transcription factor c-Fos in the primary mouse neuronal cultures after stimulation and to determine the cellular localization of human Lf and its colocalization with induced c-Fos protein. Primary dissociated cultures of hippocampal cells were obtained from the brains of newborn C57BL/6 mice (P0-P1). On day 7 of culturing, human Lf was added to the medium. After 24 h (day 8 in culture), c-Fos protein was induced in cells by triple application of 50 mM KCl. c-Fos content was analyzed using the immunofluorescent method 2 h after stimulation. Stimulation promoted exogenous Lf translocation into the nuclei of cultured neuronal cells, which correlated with increased induction of transcription factor c-Fos and was accompanied by nuclear colocalization of these proteins. These results attest to the potential of Lf as a modulator of neuronal processes and open up new prospects in studying the mechanisms of the regulatory effects of lactoferrin on cell function.

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