Role of p53 in DNA strand break-induced apoptosis in organotypic slice culture from the mouse cerebellum

• Published in: Journal of neuroscience research Vol. 60; no. 4; pp. 450 - 457
• Main Authors: Inamura, N., Araki, T., Enokido, Y., Nishio, C., Aizawa, S., Hatanaka, H.
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 15.05.2000
• Subjects: Animals; Antibiotics, Antineoplastic - pharmacology; Apoptosis - physiology; Bleomycin - pharmacology; cell cycle; Cells, Cultured; Cerebellum - cytology; Cerebellum - drug effects; Cerebellum - metabolism; Chromosome Breakage; DNA repair; In Situ Nick-End Labeling; Mice; Mice, Knockout; Mice, Mutant Strains; neuronal cell death; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; neurotrophin; programmed cell death; Proto-Oncogene Proteins c-fos - biosynthesis; Proto-Oncogene Proteins c-jun - biosynthesis; Purkinje Cells - cytology; Purkinje Cells - drug effects; Purkinje Cells - metabolism; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/(SICI)1097-4547(20000515)60:4<450::AID-JNR3>3.0.CO;2-P

Apoptosis occurs not only in mitotic cells but also in postmitotic neuronal cells. We previously suggested that the tumor suppressor gene p53 is required for DNA strand break‐induced apoptosis in dissociated culture of cerebellar granule neurons. In this study, we examined the role of p53 in apoptosis using organotypic slice culture of cerebellum from p53 null and wild‐type mice. Exposure to bleomycin significantly increased the numbers of TUNEL‐, p53‐, and c‐Jun–positive neurons in the wild‐type mouse cerebellar internal granular layer (IGL) and Purkinje cell layer (PL). However, in p53‐deficient mice, these responses were not observed. These results are consistent with our previous observations in dissociated neuronal culture showing that the amount of c‐Jun protein increases significantly after addition of bleomycin in p53 wild‐type cerebellar granule cells. The results presented here also indicate that p53 is involved in DNA strand break‐induced apoptosis of fully postmitotic central nervous system neurons and suggest that c‐Jun expression occurs downstream of p53 expression. J. Neurosci. Res. 4:450–457, 2000 © 2000 Wiley‐Liss, Inc.