)| PMID |
12618129 ( ) |
|---|---|
| Title | Mitochondrial DNA from platelets of sporadic ALS patients restores normal respiratory functions in rho(0) cells. |
| Abstract | Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, which affects the anterior horn cells of the spinal cord and cortical motor neurons. A pathophysiological role for mtDNA mutations was postulated based on the finding that cybrids obtained from mitochondria of sporadic ALS patients exhibited impaired respiratory chain activities, increased free radical scavenging enzymes, and altered calcium homeostasis. To date, however, no distinct mtDNA alterations associated with ALS have been reported. Therefore, we reexamined the hypotheses that mtDNA mutations accumulate in ALS and that cybrids generated from ALS patients' blood have impaired mitochondrial respiration. Cybrid cell lines were generated from 143B osteosarcoma rho(0) cells and platelet mitochondria of sporadic ALS patients or age-matched controls. We found no statistically significant differences in mitochondrial respiration between ALS and control cybrids, even when the electron transport chain was stressed with low concentrations of respiratory chain inhibitors. Mitochondrial respiratory chain enzyme activities were also normal in ALS cybrids, and there was no increase in free radical production. Therefore, we showed that mtDNA from platelets of ALS patients was able to restore normal respiratory function in rho(0) cells, suggesting that the presence of mtDNA mutations capable of affecting mitochondrial respiration was unlikely. University, New York, NY 10021, 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 |
|---|---|---|---|---|
| 2294 | COX8A | cytochrome c oxidase subunit 8A (ubiquitous) | 8 | COX | |
| 2422 | CS | citrate synthase | 3 | citrate synthase | |
| 31395 | COX8B | cytochrome c oxidase, subunit 8B pseudogene | 2 | cytochrome c oxidase | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 1 | superoxide dismutase 1 | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 2294 | COX8A | cytochrome c oxidase subunit 8A (ubiquitous) | COX | 1.2 | (succinate_amp_#x2013;cytochrome succinate_amp_#x2013 cytochrome c reductase IV (cytochrome cytochrome c oxidase COX and the mitochondrial matrix enzyme citrate synthase (CS) CS were |
| 2294 | COX8A | cytochrome c oxidase subunit 8A (ubiquitous) | COX | 1.2 | For example in 143B-derived cybrids COX excess capacity is such that even a stop codon mutation |
| 2294 | COX8A | cytochrome c oxidase subunit 8A (ubiquitous) | COX | 1.2 | is such that even a stop codon mutation in a COX subunit can be tolerated up to 40% heteroplasmy before an |
| 2294 | COX8A | cytochrome c oxidase subunit 8A (ubiquitous) | COX | 1.2 | Accordingly 5 _amp_#x3bc M KCN a specific inhibitor of COX was added either at the beginning of the assay ( |
| 2294 | COX8A | cytochrome c oxidase subunit 8A (ubiquitous) | COX | 1.2 | Because KCN competes with oxygen for the catalytic site on COX KCN inhibition increased to approximately 20% at O 2-50%RA |
| 2294 | COX8A | cytochrome c oxidase subunit 8A (ubiquitous) | COX | 1.2 | of the mitochondrial respiratory chain complexes I III II III COX and of the nuclear encoded mitochondrial matrix enzyme citrate synthase |
| 2294 | COX8A | cytochrome c oxidase subunit 8A (ubiquitous) | COX | 1.2 | DCFDA and incubated in medium containing increasing concentrations of the COX inhibitor KCN from 0 to 10 _amp_#x3bc M |
| 2294 | COX8A | cytochrome c oxidase subunit 8A (ubiquitous) | COX | 1.2 | NADH cytochrome c reductase II III succinate cytochrome c reductase COX cytochrome c oxidase |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase 1 | 1.0 | mitochondrial respiratory chain dysfunction was also found in transgenic mice expressing a mutant form of superoxide dismutase 1 associated with familial als [ 15 ]. |
| 2422 | CS | citrate synthase | citrate synthase | 1.0 | the activities of complex i+iii nadh_amp_#x2013;cytochrome c reductase ii+iii succinate_amp_#x2013;cytochrome c reductase iv cytochrome c oxidase cox and the mitochondrial matrix enzyme citrate synthase cs were measured as described elsewhere [ 21 ]. |
| 31395 | COX8B | cytochrome c oxidase, subunit 8B pseudogene | cytochrome c oxidase | 1.0 | the activities of complex i+iii nadh_amp_#x2013;cytochrome c reductase ii+iii succinate_amp_#x2013;cytochrome c reductase iv cytochrome c oxidase cox and the mitochondrial matrix enzyme citrate synthase cs were measured as described elsewhere [ 21 ]. |
| 2422 | CS | citrate synthase | citrate synthase | 1.0 | enzymatic activities of the mitochondrial respiratory chain complexes i+iii ii+iii cox and of the nuclear encoded mitochondrial matrix enzyme citrate synthase were measured on cybrid clones and mass cultures. |
| 2422 | CS | citrate synthase | citrate synthase | 1.0 | a respiratory chain activities in cybrid mass cultures als n = 13; controls n = 10 normalized by the activity of the mitochondrial matrix enzyme citrate synthase cs . |
| 31395 | COX8B | cytochrome c oxidase, subunit 8B pseudogene | cytochrome c oxidase | 1.0 | i+iii nadh cytochrome c reductase; ii+iii succinate cytochrome c reductase; cox cytochrome c oxidase. |