A Bax-induced pro-oxidant state is critical for cytochrome c release during programmed neuronal death. J Neurosci 2002 Aug 01;22(15):6480-90
Date
08/02/2002Pubmed ID
12151527Pubmed Central ID
PMC6758153DOI
10.1523/JNEUROSCI.22-15-06480.2002Scopus ID
2-s2.0-0036703753 (requires institutional sign-in at Scopus site) 159 CitationsAbstract
Bax is required for the apoptotic death of sympathetic neurons deprived of nerve growth factor (NGF). After NGF withdrawal, Bax translocates from the cytoplasm to the mitochondria of these cells and induces release of the proapoptotic protein cytochrome c. Here, we report that withdrawing NGF from mouse sympathetic neurons caused an increase of mitochondria-derived reactive oxygen species (ROS). Suppressing these ROS inhibited apoptosis. Bax deletion blocked death and prevented the ROS burst. Inducing a pro-oxidant state similar to that in NGF-deprived, wild-type cells caused cytochrome c release even in neurons lacking Bax. A similar ROS burst in cerebellar granule neurons undergoing apoptosis was also blocked by Bax deletion. These findings indicate that Bax lies upstream from increased ROS in NGF-deprived neurons and suggest that the Bax-induced ROS burst is both necessary and sufficient for cytochrome c redistribution in these cells.
Author List
Kirkland RA, Windelborn JA, Kasprzak JM, Franklin JLAuthor
Julia Marian Kasprzak MD Associate Professor in the Dermatology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
Cells, Cultured
Cerebellum
Cytochrome c Group
Electron Transport
Fluorescent Dyes
Heterozygote
Homozygote
Hydrogen Peroxide
Immunohistochemistry
Mice
Mice, Knockout
Mitochondria
Nerve Growth Factor
Neurons
Oxidants
Oxidation-Reduction
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-bcl-2
Reactive Oxygen Species
Superior Cervical Ganglion
Uncoupling Agents
bcl-2-Associated X Protein
