Cycloheximide induces apoptosis of astrocytes.
Cultured rat astrocytes were incubated in the presence of cycloheximide (CHX; 20 microg/mL), a potent neuroprotective agent. Then cells were subjected to DNA gel electrophoresis. Electrophoresis showed DNA ladder formation, which is characteristic of apoptosis. Inhibitors of interleukin-1beta-converting enzyme (ICE) and caspase 32(CPP32), which play critical roles in certain apoptotic pathways, did not block the cycloheximide-induced apoptosis of cultured astrocytes. This observation indicates that the role of ICE and CPP32 is not significant in the CHX-induced astrocyte apoptosis process. When the blood-brain barrier was disrupted in the rat, the number of brain cells undergoing apoptosis was significantly higher after cycloheximide administration, in contrast to controls. Of the cells that produced glial fibrillary acidic protein, some were observed to undergo apoptosis. Although CHX has been shown to be useful as a neuroprotective agent against ischemic neuronal death, astroglial toxicity may be problematic, depending on CHX concentration. Therefore, a prudent use of this compound is recommended.
Tsuchida
Takahiro
T
Department of Neurosurgery, Kansai Medical University, Osaka, Japan. tsuchida@takii.kmu.ac.jp
Kato
Takayuki
T
Yamada
Akifumi
A
Kawamoto
Keiji
K
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D001930:Brain Injuries / Q000209:etiology / Q000473:pathology; D002452:Cell Count; D002478:Cells, Cultured; D003513:Cycloheximide / Q000633:toxicity*; D004247:DNA / Q000032:analysis; D053938:DNA Fragmentation / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005615:Freezing; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D018696:Neuroprotective Agents / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D004247:DNA; D003513:Cycloheximide