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dictyNews Volume 31 Number 13
dictyNews
Electronic Edition
Volume 31, number 13
October 24, 2008
Please submit abstracts of your papers as soon as they have been
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or by using the form at
http://dictybase.org/db/cgi-bin/dictyBase/abstract_submit.
Upon publication of your paper, please send strains and plamids to
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Back issues of dictyNews, the Dicty Reference database and other
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Abstracts
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Biological activities of novel derivatives of DIF-1 isolated from Dictyostelium.
Haruhisa Kikuchi, Shinya Ishiko, Yoshiteru Oshima, Naomi Gokan, Kohei Hosaka,
and Yuzuru Kubohara*
*Gunma University IMCR, Japan.
BBRC, in press
The differentiation-inducing factor-1 (DIF-1) is a lipophilic signal molecule
(chlorinated alkylphenone) that induces stalk cell differentiation in the
cellular slime mold Dictyostelium discoideum. In addition, DIF-1 and its
derivatives have been shown to possess anti-leukemic activity and glucose
consumption-promoting activity in vitro in mammalian cells. In this study,
to assess the chemical structure-effect relationship of DIF-1, we synthesized
8 derivatives of DIF-1 and investigated their stalk cell-inducing activity in
Dictyostelium cells and pharmacological activities in mammalian cells. Of
the derivatives, two amide derivatives of DIF-1, whose hydrophobic indexes
are close to that of DIF-1, induced stalk cell differentiation as strongly
as DIF-1 in Dictyostelium cells. It was also found that some derivatives
suppressed cell growth in human K562 leukemia cells and promoted glucose
consumption in mouse 3T3-L1 cells. These results give us valuable
information as to the chemical structure-effect relationship of DIF-1.
Submitted by: Yuzuru Kubohara [kubohara@showa.gunma-u.ac.jp]
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A UDP-glucose derivative is required for vacuolar autophagic cell death
Emilie Tresse, Artemis Kosta, Corinne Giusti, Marie-Françoise Luciani
and Pierre Golstein
Autophagy, 2008, 4, 680-691
Autophagic cell death in Dictyostelium can be dissociated into a
starvation-induced sensitization stage and a death induction stage. A
UDP-glucose pyrophosphorylase (ugpB) mutant and a glycogen synthase (glcS)
mutant shared the same abnormal phenotype. In vitro, upon starvation alone
mutant cells showed altered contorted morphology, indicating that the mutations
affected the pre-death sensitization stage. Upon induction of cell death,
most of these mutant cells underwent death without vacuolization, distinct
from either autophagic or necrotic cell death. Autophagy itself was not
grossly altered as shown by conventional and electron microscopy. Exogenous
glycogen or maltose could complement both ugpB- and glcS- mutations, leading
back to autophagic cell death. The glcS- mutation could also be complemented
by 2-deoxyglucose that cannot undergo glycolysis. In agreement with the in
vitro data, upon development glcS- stalk cells died but most were not
vacuolated. We conclude that a UDP-glucose derivative (such as glycogen or
maltose) plays an essential energy-independent role in autophagic cell death.
Submitted by: Pierre Golstein [golstein@ciml.univ-mrs.fr]
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Marked mitochondrial alterations upon starvation without cell death,
caspases or Bcl-2 family members
Artemis Kosta, Marie-Françoise Luciani, Willie J.C. Geerts, Pierre Golstein
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1783,
Issue 10, October 2008, Pages 2013-2019
Dictyostelium HMX44A cells can withstand starvation under monolayer conditions
for a few days without dying. They die only when the differentiation factor
DIF-1 is exogenously added. Still, when HMX44A were subjected to starvation
without addition of DIF-1 they showed, by electron microscopy and electron
tomography, gross mitochondrial lesions including marked cristae alterations
with frequent “holes” probably originating from dilated cristae. Since these
cells did not die as shown for instance by FACS analysis, these results showed
unexpected resilience of cells bearing markedly altered mitochondria, and
thus showed that apparently destructive mitochondrial alterations may not
lead to cell death. Also, these marked mitochondrial lesions could not be
caused by caspases or bcl-2 family members, which these cells do not encode.
Submitted by: Pierre Golstein [golstein@ciml.univ-mrs.fr]
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Necrotic cell death : From reversible mitochondrial uncoupling to irreversible
lysosomal permeabilization
Corinne Giusti, Marie-Françoise Luciani, Gérard Klein, Laurence Aubry,
Emilie Tresse, Artemis Kosta, Pierre Golstein
Experimental Cell Research, In Press, Accepted Manuscript,
Available online 11 October 2008
Dictyostelium atg1- mutant cells provide an experimentally and genetically
favorable model to study necrotic cell death (NCD) with no interference
from apoptosis orautophagy. In such cells subjected to starvation and cAMP,
induction by the differentiation-inducing factor DIF or by classical
uncouplers led within minutes to mitochondrial uncoupling, which causally
initiated NCD. We now report that (1) in this model, NCD included a
mitochondrial-lysosomal cascade of events, (2) mitochondrial uncoupling
and therefore initial stages of death showed reversibility for a
surprisingly long time, (3) subsequent lysosomal permeabilization could
be demonstrated using Lysosensor blue, acridin orange, Texas red-dextran
and cathepsin B substrate, (4) this lysosomal permeabilization was
irreversible, and (5) the presence of the uncoupler was required to
maintain mitochondrial lesions but also to induce lysosomal lesions,
suggesting that signaling from mitochondria to lysosomes must be
sustained by the continuous presence of the uncoupler. These results
further characterized the NCD pathway in this priviledged model,
contributed to a definition of NCD at the lysosomal level, and suggested
that in mammalian NCD even late reversibility attempts by removal of
the inducer may be of therapeutic interest.
Submitted by: Pierre Golstein [golstein@ciml.univ-mrs.fr]
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[End dictyNews, volume 31, number 13]
