Protective effect of apoptosis-inhibitory agent, N-tosyl-L-phenylalanyl chloromethyl ketone against ischemia-induced hippocampal neuronal damage.
Delayed neuronal death in the gerbil hippocampal CA1 sector occurs 48 to 72 hours after severe forebrain ischemia. DNA fragmentation is observed in the hippocampal CA1 neurons at around that time. We show here that an inhibitor of proteolytic process of apoptosis, N-tosyl-L-phenylalanyl chloromethyl ketone (TPCK), protected hippocampal neuronal damage by inhibition of the DNA fragmentation in a dose-dependent manner and that TPCK induced an apoptosis-regulating molecule, Bcl-2 protein, in the surviving neurons. These results suggest the prevention of apoptosis-related DNA fragmentation by TPCK may be an attractive therapeutic strategy for preserving hippocampal neurons from ischemic insult.
Department of Pathology, Gifu University School of Medicine, Japan.
A
A
Hara
M
M
Niwa
M
M
Nakashima
T
T
Iwai
T
T
Uematsu
N
N
Yoshimi
H
H
Mori
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D016548:Prosencephalon / Q000098:blood supply*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology*
D019253:Proto-Oncogene Proteins c-bcl-2; D015842:Serine Proteinase Inhibitors; D014108:Tosylphenylalanyl Chloromethyl Ketone