PMID- 9539784
OWN - NLM
STAT- MEDLINE
DCOM- 19980513
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 95
IP  - 8
DP  - 1998 Apr 14
TI  - Different mechanisms for suppression of apoptosis by cytokines and calcium 
      mobilizing compounds.
PG  - 4601-6
AB  - Overexpression of wild-type p53 in M1 myeloid leukemia cells induces apoptotic 
      cell death that was suppressed by the calcium ionophore A23187 and the calcium 
      ATPase inhibitor thapsigargin (TG). This suppression of apoptosis by A23187 or TG 
      was associated with suppression of caspase activation but not with suppression of 
      wild-type-p53-induced expression of WAF-1, mdm-2, or FAS. In contrast to 
      suppression of apoptosis by the cytokines interleukin 6 (IL-6) and interferon 
      gamma, a protease inhibitor, or an antioxidant, suppression of apoptosis by 
      A23187 or TG required extracellular Ca2+ and was specifically abolished by the 
      calcineurin inhibitor cyclosporin A. IL-6 induced immediate early activation of 
      junB and zif/268 (Egr-1) but A23187 and TG did not. A23187 and TG also suppressed 
      induction of apoptosis by doxorubicin or vincristine in M1 cells that did not 
      express p53 by a cyclosporin A-sensitive mechanism. Suppression of apoptosis by 
      A23187 or TG was not associated with autocrine production of IL-6. Apoptosis 
      induced in IL-6-primed M1 cells after IL-6 withdrawal was not suppressed by 
      A23187 or TG but was suppressed by the cytokines IL-6, IL-3, or interferon gamma. 
      The results indicate that these Ca2+-mobilizing compounds can suppress some 
      pathways of apoptosis suppressed by cytokines but do so by a different mechanism.
FAU - Lotem, J
AU  - Lotem J
AD  - Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, 
      Israel.
FAU - Sachs, L
AU  - Sachs L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cdkn1a protein, mouse)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Cyclins)
RN  - 0 (Cytokines)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (fas Receptor)
RN  - 37H9VM9WZL (Calcimycin)
RN  - 5J49Q6B70F (Vincristine)
RN  - 67526-95-8 (Thapsigargin)
RN  - 80168379AG (Doxorubicin)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - EC 2.3.2.27 (Mdm2 protein, mouse)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/toxicity
MH  - Apoptosis/*drug effects
MH  - Calcimycin/*pharmacology
MH  - Calcium/*metabolism
MH  - Cell Survival/drug effects
MH  - Cyclin-Dependent Kinase Inhibitor p21
MH  - Cyclins/biosynthesis
MH  - Cyclosporine/pharmacology
MH  - Cysteine Endopeptidases/metabolism
MH  - Cytokines/*pharmacology
MH  - Doxorubicin/toxicity
MH  - Enzyme Inhibitors/metabolism/pharmacology
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Genes, p53
MH  - Kinetics
MH  - Leukemia, Myeloid
MH  - Mice
MH  - Neoplasms, Experimental
MH  - *Nuclear Proteins
MH  - Proto-Oncogene Proteins/biosynthesis
MH  - Proto-Oncogene Proteins c-mdm2
MH  - Recombinant Proteins/pharmacology
MH  - Thapsigargin/*pharmacology
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Protein p53/biosynthesis
MH  - Vincristine/toxicity
MH  - fas Receptor/biosynthesis
PMC - PMC22536
EDAT- 1998/05/16 00:00
MHDA- 1998/05/16 00:01
PMCR- 1998/10/14
CRDT- 1998/05/16 00:00
PHST- 1998/05/16 00:00 [pubmed]
PHST- 1998/05/16 00:01 [medline]
PHST- 1998/05/16 00:00 [entrez]
PHST- 1998/10/14 00:00 [pmc-release]
AID - 0452 [pii]
AID - 10.1073/pnas.95.8.4601 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4601-6. doi: 10.1073/pnas.95.8.4601.