Overexpression of SOD1 protects vulnerable motor neurons after spinal cord injury by attenuating mitochondrial cytochrome c release.

Abstract

Defective Cu,Zn-superoxide dismutase (SOD1) is responsible for some types of amyotrophic lateral sclerosis, and ventral horn motor neurons (VMN) have been shown to die through a mitochondria-dependent apoptotic pathway after chronic exposure to high levels of reactive oxygen species (ROS). VMN are also selectively vulnerable to mild spinal cord injury (SCI); however, the involvement of SOD1, ROS, and apoptosis in their death has not been clarified. Mild compression SCI was induced in SOD1-overexpressing transgenic rats and wild-type littermates. Superoxide production, mitochondrial release of cytochrome c, and activation of caspase-9 were examined, and apoptotic DNA injury was also characterized. In the wild-type animals, increased superoxide production, mitochondrial release of cytochrome c, and cleaved caspase-9 were observed exclusively in VMN after SCI. Subsequently, a majority of VMN (75%) selectively underwent delayed apoptotic cell death. Transgenic animals showed less superoxide production, mitochondrial cytochrome c release, and caspase-9 activation, resulting in death of only 45% of the VMN. These results suggest that the ROS-initiated mitochondrial signaling pathway possibly plays a pivotal role in apoptotic VMN death after SCI and that increased levels of SOD1 in VMN reduce oxidative stress, thereby attenuating the activation of the pathway and delayed cell death.

• Authors: Taku Sugawara, Anders Lewén, Yvan Gasche, Fengshan Yu, Pak H Chan
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 16 Issue 14 Pg. 1997-9 (Dec 2002) ISSN: 1530-6860 [Electronic] United States
• PMID: 12368231 (Publication Type: Journal Article)

Chemical References

• Cytochrome c Group
• Superoxides
• Sod1 protein, rat
• Superoxide Dismutase
• Superoxide Dismutase-1

Topics

• Animals
• Animals, Genetically Modified
• Apoptosis
• Cell Nucleus (ultrastructure)
• Cytochrome c Group (metabolism)
• Cytoprotection
• DNA Fragmentation
• Mitochondria (metabolism)
• Models, Biological
• Motor Neurons (metabolism, pathology, ultrastructure)
• Rats
• Spinal Cord (chemistry)
• Spinal Cord Diseases (metabolism, pathology)
• Superoxide Dismutase (genetics, metabolism, physiology)
• Superoxide Dismutase-1
• Superoxides (metabolism)