Multimeric alpha-lactalbumin from human milk induces apoptosis through a direct effect on cell nuclei
Author
Summary, in English
A fraction from human milk containing spf-multimer alpha-lactalbumin (MAL) induces apoptosis in tumor cells and immature cells but spares mature cells. The mechanism of apoptosis induction and the molecular basis for the difference in susceptibility between tumor cells and healthy cells have not been defined. In this study we examined the interaction of MAL with different cellular compartments, using confocal microscopy and subcellular fractionation. MAL was shown to accumulate in the nuclei of sensitive cells rather than in the cytosol, the vesicular fraction, or the ER-Golgi complex. Nuclear uptake occurred rapidly in cells that were susceptible to the apoptosis-inducing effect, but not in nuclei of resistant cells. Nuclear uptake was through the nuclear pore complex and was critical for the induction of DNA fragmentation, since inhibition of nuclear uptake with WGA rescued digitonin-permeabilized cells from induction of DNA fragmentation. Ca2+ was required for MAL-induced DNA fragmentation but nuclear uptake of MAL was independent of Ca2+. This way MAL differs from most previously described agents in that it crosses the plasma membrane and cytosol, and enters cell nuclei where it induces DNA fragmentation through a direct effect at the nuclear level.
Department/s
Publishing year
1999-02-01
Language
English
Pages
60-451
Publication/Series
Experimental Cell Research
Volume
246
Issue
2
Document type
Journal article
Publisher
Academic Press
Topic
- Cell and Molecular Biology
Keywords
- Animals
- Apoptosis
- Calcium
- Cell Nucleus
- Cells, Cultured
- DNA Fragmentation
- Humans
- Intracellular Fluid
- Lactalbumin
- Mice
- Milk, Human
- Nuclear Envelope
- Tumor Cells, Cultured
Status
Published
Research group
- Experimental Infection Medicine, Malmö
- Pediatric Nephrology
ISBN/ISSN/Other
- ISSN: 0014-4827