Nuclear factor-kappa B-dependent cyclin D1 induction and DNA replication associated with N-methyl-D-aspartate receptor-mediated apoptosis in rat striatum

作者：Liang Zhorig Qin; Wang Xiaoxia; Li Ling Yun; Wang Yumei; Chen Ren Wu; Chuang De Maw; Chase Thomas N; Qin Zheng Hong^*

来源：Journal of Neuroscience Research, 2007, 85(6): 1295-1309.

DOI：10.1002/jnr.21248

• excitotoxicity
• apoptosis
• NF-kappa B
• cell cycle
• cyclin D1
• DNA replication

Cell cycle reentry has been found during apoptosis of postmitotic neurons under certain pathological conditions. To evaluate whether nuclear factor-kappa B (NF-kappa B) activation promotes cell cycle entry and neuronal apoptosis, we studied the relation among NF-kappa B-mediated cyclin induction, bromodeoxyuridine (BrdU) incorporation, and apoptosis initiation in rat striatal neurons following excitotoxic insult. Intrastriatally injected N-methyl-D-aspartate receptor agonist quinolinic acid (QA, 60 nmol) elicited a rise in cyclin D1 mRNA and protein levels (P < 0.05). QA-induced NF-kappa B activation occurred in striatal neurons and nonneuronal cells and partially colocalized with elevated cyclin D1 immunoreactivity and TUNEL-positive nuclei. QA triggered DNA replication as evidenced by BrdU incorporation; some striatal BrdU-positive cells were identified as neurons by colocalization with NeuN. Blockade of NF-kappa B nuclear translocation with the recombinant peptide NF-kappa B SN50 attenuated the QA-induced elevation in cyclin D1 and BrdU incorporation. QA-induced internucleosomal DNA fragmentation was blunted by G(1)/S-phase cell cycle inhibitors. These findings suggest that NF-kappa B activation stimulates cyclin D1 expression and triggers DNA replication in striatal neurons. Excitotoxin-induced neuronal apoptosis may thus result from, at least partially, a failed cell cycle attempt.

• 出版日期2007-5-1
• 单位苏州大学