부산대학교 도서관

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1460-9568.2007.05381.x Byline: Karl-Heinz Herzog (1), Adriana Schulz (1), Corina Buerkle (1), Christian Gromoll (2), Johann S. Braun (3,4) Keywords: caspase; caspase-independent; cerebellum; [gamma]-irradiation; mouse retina Abstract: Abstract Caspases are important executioners of the endogenous cell death program. However, their function is not restricted to the induction of cell death. Caspases may process cytokines and contribute to cell differentiation or lymphocyte proliferation. In addition to their pleiotropic functions we show evidence that, under certain conditions, caspases are activated during apoptosis without executing the cell death program. Following whole body irradiation, p53 and caspases were activated in both the cerebellum and eye of postnatal day 5 mice. Although p53 activation and cell death kinetics were similar in both the cerebellum and eye, the processing of caspases was protracted and reduced in the eye. In particular, retinal caspase activation appeared not to be the executioner of cell death; incubation of retinal and cerebellar explants in the presence of the pan-caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone prevented DNA fragmentation, a hallmark of apoptosis, only in cerebellar granule cells. In contrast, in retinal cells no impairment of DNA fragmentation was observed in the presence of N-benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone, indicating p53-dependent but caspase-independent cell death pathways despite caspase activation. Author Affiliation: (1)Institute for Genetics, University of Stuttgart-Hohenheim, Garbenstrasse 30, D-70599 Stuttgart, Germany (2)Marienhospital Stuttgart, Stuttgart, Germany (3)Humboldt University, Charite University Hospital, Department of Experimental Neurology, Berlin, Germany (4)United Arab Emirates University, Faculty of Medicine and Health Sciences, Al Ain, United Arab Emirates Article History: Received 16 February 2006, revised 30 November 2006, accepted 1 January 2007 Article note: Dr K.-H. Herzog, as above., E-mail: khherzog@uni-hohenheim.de