)| PMID |
9172131 ( ) |
|---|---|
| Title | Evidence of reduced DNA repair in amyotrophic lateral sclerosis brain tissue. |
| Abstract | Oxidative stress is proposed to play a central role in the pathogenesis of amyotrophic lateral sclerosis (ALS). Anti-oxidant enzymes and DNA repair proteins are two major mechanisms by which cells counteract the deleterious effects of reactive oxygen species (ROS). Neurons may be particularly vulnerable to ROS-induced oxidative DNA damage; this is repaired by the base-excision repair (BER) pathway. Frontal cortical levels and activity of the pivotal BER protein apurinic/apyrimidinic endonuclease (APE) were determined in 11 patients with sporadic ALS and six age-matched control subjects. APE levels (p < 0.003) and activity (p < 0.000007) were significantly lower in ALS subjects than in controls. These findings suggest that ALS brain tissue is inefficient in repairing oxidative DNA damage. Health Sciences University, Portland 97201, USA. |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | 31 | apurinic/apyrimidinic endonuclease | ape 1 | APE | |
| 7211 | MPG | N-methylpurine-DNA glycosylase | 8 | n methylpurine dna glycosylase mpg | MPG | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 2 | SOD1 | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | of the pivotal BER protein apurinic/apyrimidinic apurinic apyrimidinic endonuclease (APE) APE were determined in 11 patients with sporadic ALS and six |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | APE levels ( p _amp_#60 0.003 and activity ( p _amp_#60 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.9 | major cellular antioxidant enzyme Cu/Zn Cu Zn superoxide dismutase (SOD1) SOD1 in familial ALS subjects 3 has initiated an intense investigation |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.9 | fewer than 20_amp_#37 of familial ALS cases map to the SOD1 gene |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | abasic site is repaired by apurinic/apyrimidinic apurinic apyrimidinic endonuclease (APE) APE |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | APE the pivotal step in BER is found in both the |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | mitochondria (~65 ~65 kDa 10 A reduction or loss of APE would be extremely detrimental to a neuron and could conceivably |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | APE is a bifunctional protein with separate domains for DNA repair |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | Therefore APE possesses multiple cellular functions and its deficiency could have profound |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | In fact lack of the APE gene is lethal to embryonic mutant mice (gestational gestational day |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | The present study aimed to determine whether the BER protein APE is deficient in the brains of ALS subjects |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | APE levels were determined in human brain tissue extracts and compared |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | of HeLa cells (positive positive control and with recombinant human APE (a a hist_amp_#237 dine-tagged full-length human protein provided by Dr |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | APE activity was determined in human brain tissue extracts by measuring |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | APE levels and activity (ability ability to repair apurinic sites in |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | There was no significant correlation between post mortem interval and APE levels in control ( r _amp_#61 _amp_#45 0.5 or ALS |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | Cortical APE levels were reduced by 3-4_amp_#215 3 ( p _amp_#60 0.003 |
| 7211 | MPG | N-methylpurine-DNA glycosylase | MPG | 1.1 | to the human BER protein N -methylpurine DNA glycosylase (MPG) MPG and purified human MPG (positive positive control (both both provided |
| 7211 | MPG | N-methylpurine-DNA glycosylase | MPG | 1.1 | protein N -methylpurine DNA glycosylase (MPG) MPG and purified human MPG (positive positive control (both both provided by Dr Sankar Mitra |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | In contrast to APE levels cortical MPG levels in ALS subjects were not significantly |
| 7211 | MPG | N-methylpurine-DNA glycosylase | MPG | 1.1 | In contrast to APE levels cortical MPG levels in ALS subjects were not significantly different ( p |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | Like APE levels APE activity was significantly lower ( p _amp_#60 0.000007 |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | Like APE levels APE activity was significantly lower ( p _amp_#60 0.000007 in ALS |
| 7211 | MPG | N-methylpurine-DNA glycosylase | MPG | 1.1 | removed by a DNA glycosylase (e.g e.g formamidopyrimidine DNA glycosylase MPG 20 21 and the resulting apurinic site repaired by APE |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | MPG 20 21 and the resulting apurinic site repaired by APE 8-Oxodeoxyguanosine levels are elevated in ALS spinal cord tissue 6 |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | from the present studies indicate that the pivotal BER protein APE is severely deficient in ALS brain tissue |
| 7211 | MPG | N-methylpurine-DNA glycosylase | MPG | 1.1 | The lack of a similar reduction in the BER protein MPG in ALS brain tissue suggests a selective abnormality in APE |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | MPG in ALS brain tissue suggests a selective abnormality in APE |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | Interestingly APE activity has also been examined in lymphocytes from patients with |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | a double-stranded oligonucleotide probe containing a single AP site 22 APE activity was shown to be similarly reduced in lymphocytes of |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | A similar reduction of APE in both ALS brain and lymphocyte tissue 22 suggests that |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | deficit is systemic and possibly due to an abnormality in APE regulation or a gene mutation |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | APE | 3.9 | Detection of several missense APE gene mutations 22 in lymphocyte DNA from patients with sporadic |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | apurinic/apyrimidinic endonuclease | 1.0 | frontal cortical levels and activity of the pivotal ber protein apurinic/apyrimidinic endonuclease ape were determined in 11 patients with sporadic als and six age matched control subjects. |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | apurinic/apyrimidinic endonuclease | 1.0 | frontal cortical levels and activity of the pivotal ber protein apurinic/apyrimidinic endonuclease ape were determined in 11 patients with sporadic als and six age matched control subjects. |
| 7211 | MPG | N-methylpurine-DNA glycosylase | n methylpurine dna glycosylase | 1.0 | dna base excision repair ber is considered to be the predominant pathway for repair of oxidative dna damage. 9 the damaged base is removed by a glycosylase e.g formamidopyrimidine or n methylpurine dna glycosylase and the resulting abasic site is repaired by apurinic/apyrimidinic endonuclease ape . |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | apurinic/apyrimidinic endonuclease | 1.0 | inant pathway for repair of oxidative dna damage. 9 the damaged base is removed by a glycosylase e.g formamidopyrimidine or n methylpurine dna glycosylase and the resulting abasic site is repaired by apurinic/apyrimidinic endonuclease ape . |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | apurinic/apyrimidinic endonuclease | 1.0 | inant pathway for repair of oxidative dna damage. 9 the damaged base is removed by a glycosylase e.g formamidopyrimidine or n methylpurine dna glycosylase and the resulting abasic site is repaired by apurinic/apyrimidinic endonuclease ape . |
| 587 | APEX1 | APEX nuclease (multifunctional DNA repair enzyme) 1 | ape 1 | 1.0 | membranes were immunoprobed by incubating blots with blocking solution containing anti ape 1:2000 for 1 h at room temperature. |
| 7211 | MPG | N-methylpurine-DNA glycosylase | n methylpurine dna glycosylase | 1.0 | for comparison protein extracts 50 microg from several control n _amp_#61; 4 and als n _amp_#61; 3 subjects were analyzed by western blotting using a monoclonal antibody to the human ber protein n methylpurine dna glycosylase mpg and purified human mpg positive control both provided by dr sankar mitra utmb galveston tx . |
| 7211 | MPG | N-methylpurine-DNA glycosylase | n methylpurine dna glycosylase mpg | 1.0 | for comparison protein extracts 50 microg from several control n _amp_#61; 4 and als n _amp_#61; 3 subjects were analyzed by western blotting using a monoclonal antibody to the human ber protein n methylpurine dna glycosylase mpg and purified human mpg positive control both provided by dr sankar mitra utmb galveston tx . |