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Multimeric alpha-lactalbumin from human milk induces apoptosis through a direct effect on cell nuclei

Håkansson, Anders P LU ; Andréasson, J LU ; Zhivotovsky, B; Karpman, D LU ; Orrenius, S and Svanborg, C LU (1999) In Experimental Cell Research 246(2). p.451-60
Abstract

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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Apoptosis, Calcium, Cell Nucleus, Cells, Cultured, DNA Fragmentation, Humans, Intracellular Fluid, Lactalbumin, Mice, Milk, Human, Nuclear Envelope, Tumor Cells, Cultured
in
Experimental Cell Research
volume
246
issue
2
pages
10 pages
publisher
Academic Press
external identifiers
  • Scopus:0037584357
ISSN
0014-4827
DOI
10.1006/excr.1998.4265
language
English
LU publication?
yes
id
4dace6a8-95bb-411a-adb4-6d9303f500c2
date added to LUP
2016-05-21 11:30:18
date last changed
2016-06-09 14:47:37
@misc{4dace6a8-95bb-411a-adb4-6d9303f500c2,
  abstract     = {<p>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.</p>},
  author       = {Håkansson, Anders P and Andréasson, J and Zhivotovsky, B and Karpman, D and Orrenius, S and Svanborg, C},
  issn         = {0014-4827},
  keyword      = {Animals,Apoptosis,Calcium,Cell Nucleus,Cells, Cultured,DNA Fragmentation,Humans,Intracellular Fluid,Lactalbumin,Mice,Milk, Human,Nuclear Envelope,Tumor Cells, Cultured},
  language     = {eng},
  month        = {02},
  number       = {2},
  pages        = {451--60},
  publisher    = {ARRAY(0x8722990)},
  series       = {Experimental Cell Research},
  title        = {Multimeric alpha-lactalbumin from human milk induces apoptosis through a direct effect on cell nuclei},
  url          = {http://dx.doi.org/10.1006/excr.1998.4265},
  volume       = {246},
  year         = {1999},
}