Abstract
Cell shrinkage and loss of cell viability by apoptosis have been examined in cultured CD95(Fas/Apo-1)-expressing leukemia-derived CEM and HL-60 cells subjected to acute deprivation of glutamine, a major compatible osmolyte engaged in cell volume control. Glutamine deprivation-mediated cell shrinkage promoted a ligand-independent activation of the CD95-mediated apoptotic pathway. Cell transfection with plasmids expressing FADD-DN or v-Flip viral proteins pointed to a functional clustering of CD95 receptors at the cell surface with activation of the 'extrinsic pathway' caspase cascade. Accordingly, cell shrinkage did not induce apoptosis in CD95 receptor-negative lymphoma L1210 cells. Replacement of glutamine with surrogate compatible osmolytes counteracted cell volume decrement and protected the CD95-expressing cells from apoptosis. A glutamine deprivation-dependent cell shrinkage with activation of the CD95-mediated pathway was also observed when asparaginase was added to the medium. Asparagine depletion had no role in this process. The cell-size shrinkage-dependent apoptosis induced by glutamine restriction in CD95-expressing leukemic cells may therefore be of clinical relevance in amidohydrolase enzyme therapies.
| Original language | English |
|---|---|
| Pages (from-to) | 1004-1013 |
| Number of pages | 10 |
| Journal | Cell Death and Differentiation |
| Volume | 8 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2001 |
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Keywords
- Apoptosis
- Asparaginase
- CD95 (Fas/Apo-1) receptor
- Cell-shrinkage
- Glutamine
ASJC Scopus subject areas
- Cell Biology
Cite this
Glutamine deprivation-mediated cell shrinkage induces ligand-independent CD95 receptor signaling and apoptosis. / Fumarola, C.; Zerbini, A.; Guidotti, G. G.
In: Cell Death and Differentiation, Vol. 8, No. 10, 2001, p. 1004-1013.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Glutamine deprivation-mediated cell shrinkage induces ligand-independent CD95 receptor signaling and apoptosis
AU - Fumarola, C.
AU - Zerbini, A.
AU - Guidotti, G. G.
PY - 2001
Y1 - 2001
N2 - Cell shrinkage and loss of cell viability by apoptosis have been examined in cultured CD95(Fas/Apo-1)-expressing leukemia-derived CEM and HL-60 cells subjected to acute deprivation of glutamine, a major compatible osmolyte engaged in cell volume control. Glutamine deprivation-mediated cell shrinkage promoted a ligand-independent activation of the CD95-mediated apoptotic pathway. Cell transfection with plasmids expressing FADD-DN or v-Flip viral proteins pointed to a functional clustering of CD95 receptors at the cell surface with activation of the 'extrinsic pathway' caspase cascade. Accordingly, cell shrinkage did not induce apoptosis in CD95 receptor-negative lymphoma L1210 cells. Replacement of glutamine with surrogate compatible osmolytes counteracted cell volume decrement and protected the CD95-expressing cells from apoptosis. A glutamine deprivation-dependent cell shrinkage with activation of the CD95-mediated pathway was also observed when asparaginase was added to the medium. Asparagine depletion had no role in this process. The cell-size shrinkage-dependent apoptosis induced by glutamine restriction in CD95-expressing leukemic cells may therefore be of clinical relevance in amidohydrolase enzyme therapies.
AB - Cell shrinkage and loss of cell viability by apoptosis have been examined in cultured CD95(Fas/Apo-1)-expressing leukemia-derived CEM and HL-60 cells subjected to acute deprivation of glutamine, a major compatible osmolyte engaged in cell volume control. Glutamine deprivation-mediated cell shrinkage promoted a ligand-independent activation of the CD95-mediated apoptotic pathway. Cell transfection with plasmids expressing FADD-DN or v-Flip viral proteins pointed to a functional clustering of CD95 receptors at the cell surface with activation of the 'extrinsic pathway' caspase cascade. Accordingly, cell shrinkage did not induce apoptosis in CD95 receptor-negative lymphoma L1210 cells. Replacement of glutamine with surrogate compatible osmolytes counteracted cell volume decrement and protected the CD95-expressing cells from apoptosis. A glutamine deprivation-dependent cell shrinkage with activation of the CD95-mediated pathway was also observed when asparaginase was added to the medium. Asparagine depletion had no role in this process. The cell-size shrinkage-dependent apoptosis induced by glutamine restriction in CD95-expressing leukemic cells may therefore be of clinical relevance in amidohydrolase enzyme therapies.
KW - Apoptosis
KW - Asparaginase
KW - CD95 (Fas/Apo-1) receptor
KW - Cell-shrinkage
KW - Glutamine
UR - http://www.scopus.com/inward/record.url?scp=0034771851&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034771851&partnerID=8YFLogxK
U2 - 10.1038/sj.cdd.4400902
DO - 10.1038/sj.cdd.4400902
M3 - Article
C2 - 11598798
AN - SCOPUS:0034771851
VL - 8
SP - 1004
EP - 1013
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
SN - 1350-9047
IS - 10
ER -