Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

Increased Hydroxyl Radical Production and Apoptosis in PC12 Neuron Cells Expressing the Gain-of-Function Mutant G93A SOD1 Gene

Rugao Liu, Rama Krishna Narla, Igor Kurinov, Baolin Li and Fatih M. Uckun
Radiation Research
Vol. 151, No. 2 (Feb., 1999), pp. 133-141
DOI: 10.2307/3579763
Stable URL: http://www.jstor.org/stable/3579763
Page Count: 9
  • Read Online (Free)
  • Download ($10.00)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Increased Hydroxyl Radical Production and Apoptosis in PC12 Neuron Cells Expressing the Gain-of-Function Mutant G93A SOD1 Gene
Preview not available

Abstract

Mutations of the SOD1 gene (formerly known as Cu,Zn-SOD) are frequently associated with the familial form of amyotrophic lateral sclerosis (ALS). The G93A mutation of SOD1 with substitution of Gly to Ala at residue 93 results in gain of a peroxidative function. Here we report that transfection of PC12 neuron precursor cells with the G93A mutation of SOD1 results in increased production of hydroxyl radicals (· OH) and an enhanced rate of cell death by apoptosis. Notably, PC12 cells transfected with the H63C/G93A mutant of SOD1 with a mutation in the catalytic site that converts histidine at position 63 to cysteine showed a dramatically reduced production of · OH and rate of death by apoptosis. Thus the gain of function of the mutant G93A SOD1 can be reduced by an active site mutation. These results provide additional genetic evidence for the hypothesis that the increased · OH production and induced cytotoxicity in neuron cells expressing the mutant G93A SOD1 results from the gain of peroxidative function by the enzyme's catalytic site.

Page Thumbnails

  • Thumbnail: Page 
133
    133
  • Thumbnail: Page 
134
    134
  • Thumbnail: Page 
135
    135
  • Thumbnail: Page 
136
    136
  • Thumbnail: Page 
137
    137
  • Thumbnail: Page 
138
    138
  • Thumbnail: Page 
139
    139
  • Thumbnail: Page 
140
    140
  • Thumbnail: Page 
141
    141