Kainic acid-induced apoptosis in cerebellar granule neurons: an attempt at cell cycle re-entry.
This study was undertaken to investigate whether kainic acid (KA) may regulate the expression of several proteins which plays an important role in cell-cycle progression in cerebellar granule neurons (CGNs). KA induced decrease in MTT values in a concentration dependent way. Flow cytometric analysis showed that KA was able to induce 30% apoptosis in CGNs. Apoptotic nuclear condensation were detected 24 h of exposure to KA (200 microM). An associated marked increase in DNA synthesis, measured by BrdU incorporation, was observed. Western blot analysis showed that KA induced an increase in the expression of Cdk2, cyclin E and E2F-1. It is proposed that, in post-mitotic cells like CGNs, re-entry cell cycle could be responsible for the apoptotic effect of KA.
Verdaguer
Ester
E
Unitat de Farmacologia i Farmacognósia, Facultat de Farmàcia, Universitat de Barcelona, Nucli Universitari de Pedralbes, E-08028 Barcelona, Spain.
García-Jordà
Elvira
E
Canudas
Anna M
AM
Domínguez
Esther
E
Jiménez
Andrés
A
Pubill
David
D
Escubedo
Elena
E
Pallàs
Jorge Camarasa Mercè
JC
Camins
Antoni
A
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D018797:Cell Cycle Proteins; D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid