Trifluoromethyl ketones show culture age-dependent inhibitory effects on low K(+)-induced apoptosis in cerebellar granule neurons.
We previously reported that two trifluoromethyl ketones, 3,3,3-trifluoro-1-phenyl-1,2-propanedione (TF1) and 1,1,1-trifluoro-3-phenyl-2-propanone (TF2), have neuroprotective effects against low K(+)-induced apoptosis in cerebellar granule neurons (CGNs) exposed at 12-13 days in vitro (DIV). On the other hand, these compounds showed weak neuroprotective potency against 7 DIV CGNs. It is reported that actinomycin D (Act-D), cycloheximide (CHX), and caspase-3 inhibitors prevent the apoptosis of CGNs induced by K+ deprivation. However, these experiments are generally performed using 7 DIV CGNs. We investigated and compared the antiapoptotic efficacy of these drugs and newly-discovered TF1 and TF2 to protect DIV 7 and 12-13 CGNs from death induced by K+ deprivation. Apoptosis of CGNs induced by K+ withdrawal at 13 DIV was potently inhibited by Act-D and CHX similar to those at 7 DIV. Caspase-3 inhibitors moderately suppressed cell death during low K(+)-induced apoptosis both exposed 7 and 13 DIV. Serine protease inhibitor N-tosyl-L-phenylalanyl chloromethylketone (TPCK) had no effect on K(+)-deprivation-induced apoptosis of CGNs at both 7 and 12 DIV. This study showed that there are different pathways of apoptosis in CGNs depending on the culture age.
Sunaga
Katsuyoshi
K
Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama 350-0295, Japan. ksunaga@josai.ac.jp
Tanaka
Toru
T
Tani
Satoru
S
Kawase
Masami
M
D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D002531:Cerebellum / Q000254:growth & development*; D003513:Cycloheximide / Q000494:pharmacology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D003609:Dactinomycin; D003513:Cycloheximide; C505410:Casp3 protein, rat; D053148:Caspase 3; D011188:Potassium