TY - JOUR
T1 - Anti-apoptotic actions of cycloheximide
T2 - Blockade of programmed cell death or induction of programmed cell life?
AU - Mattson, M. P.
AU - Furukawa, K.
N1 - Funding Information:
We thank S. Estus, W. Fu, and R. J. Mark for their important contributions to our studies of mechanisms of CHX action. Supported by grants to M. P. M. from the NIH (NS29001 and NS30583) and the Alzheimer’s Association.
PY - 1997
Y1 - 1997
N2 - Cycloheximide (CHX), long recognized for its ability to inhibit protein synthesis, has been widely employed in studies of cell death to the extent that prevention of cell death by CHX has been used as prima facie evidence for a subtype of apoptosis called 'programmed cell death'. However, very rarely have investigators determined the effects of CHX on protein synthesis in their particular cell death paradigms. Recent findings are revealing alternative mechanisms of action of CHX that involve, ironically, stimulation of cytoprotective signalling pathways. For example, in embryonic rat hippocampal cell cultures CHX protects neurons against oxidative insults by a mechanism involving induction of neuroprotective gene products including Bcl-2. CHX induces increases in immediate early gene mRNA levels, and can activate several different kinases and transcription factors that are also activated by various insults and in response to anti-apoptotic growth factors. Concentrations of CHX that cause only a modest and/or transient decrease in overall protein synthesis may prevent cell death by inducing cytoprotective signalling pathways ('programmed cell life'), whereas higher concentrations of CHX may prevent cell death by blocking the expression of 'death genes'. Establishing which of these anti-apoptotic mechanisms of action of CHX is operative in each cell death paradigm is clearly essential for proper interpretation of experimental results.
AB - Cycloheximide (CHX), long recognized for its ability to inhibit protein synthesis, has been widely employed in studies of cell death to the extent that prevention of cell death by CHX has been used as prima facie evidence for a subtype of apoptosis called 'programmed cell death'. However, very rarely have investigators determined the effects of CHX on protein synthesis in their particular cell death paradigms. Recent findings are revealing alternative mechanisms of action of CHX that involve, ironically, stimulation of cytoprotective signalling pathways. For example, in embryonic rat hippocampal cell cultures CHX protects neurons against oxidative insults by a mechanism involving induction of neuroprotective gene products including Bcl-2. CHX induces increases in immediate early gene mRNA levels, and can activate several different kinases and transcription factors that are also activated by various insults and in response to anti-apoptotic growth factors. Concentrations of CHX that cause only a modest and/or transient decrease in overall protein synthesis may prevent cell death by inducing cytoprotective signalling pathways ('programmed cell life'), whereas higher concentrations of CHX may prevent cell death by blocking the expression of 'death genes'. Establishing which of these anti-apoptotic mechanisms of action of CHX is operative in each cell death paradigm is clearly essential for proper interpretation of experimental results.
KW - Antioxidant enzymes
KW - Apoptosis
KW - Bcl-2
KW - Free radicals
KW - NF-κB
KW - Protein synthesis
KW - Transcription factors
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U2 - 10.1023/A:1026433019210
DO - 10.1023/A:1026433019210
M3 - Article
C2 - 14646539
AN - SCOPUS:0000333909
VL - 2
SP - 257
EP - 264
JO - Apoptosis : an international journal on programmed cell death
JF - Apoptosis : an international journal on programmed cell death
SN - 1360-8185
IS - 3
ER -