Gly482Ser PGC-1a gene polymorphism and exercise-related oxidative stress in Amyotrophic Lateral Sclerosis patients
The role of exercise in Amyotrophic Lateral Sclerosis (ALS) pathogenesis is controversial and unclear. Exercise induces a pleiotropic adaptive response in skeletal muscle, largely through the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a transcriptional coactivator that reg...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-04-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fncel.2016.00102/full |
| _version_ | 1811262994387042304 |
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| author | Angelique ePasquinelli Lucia eChico Livia ePasquali Costanza eBisordi Annalisa eLo Gerfo Monica eFabbrini Lucia ePetrozzi Letizia eMarconi Elena eCaldarazzo Ienco Michelangelo eMancuso Gabriele eSiciliano |
| author_facet | Angelique ePasquinelli Lucia eChico Livia ePasquali Costanza eBisordi Annalisa eLo Gerfo Monica eFabbrini Lucia ePetrozzi Letizia eMarconi Elena eCaldarazzo Ienco Michelangelo eMancuso Gabriele eSiciliano |
| author_sort | Angelique ePasquinelli |
| collection | DOAJ |
| description | The role of exercise in Amyotrophic Lateral Sclerosis (ALS) pathogenesis is controversial and unclear. Exercise induces a pleiotropic adaptive response in skeletal muscle, largely through the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a transcriptional coactivator that regulates mitochondrial biogenesis and antioxidant defense mechanisms. It has been suggested that a Gly482Ser substitution in PGC-1α has functional relevance in human disorders and in athletic performance. To test this hypothesis, we examined the genotype distribution of PGC-1α Gly482Ser (1444 G>A) in ALS patients to evaluate whether or not the minor serine-encoding allele 482Ser is involved in oxidative stress responses during physical exercise. We genotyped 197 sporadic ALS patients and 197 healthy controls in order to detect differences in allelic frequencies and genotype distribution between the two groups. A total of 74 ALS patients and 65 controls were then comparatively assessed for plasmatic levels of the oxidative stress biomarkers, advanced oxidation protein products, ferric reducing ability and thiol groups. In addition a subgroup of 35 ALS patients were also assessed for total SOD and catalase plasmatic activity. Finally in 28 ALS patients we evaluated the plasmatic curve of the oxidative stress biomarkers and lactate during an incremental exercise test. No significant differences were observed in the genotype distribution and allelic frequency in ALS patients compared to the controls. We found significant increased advanced oxidation protein products (p<0.001) and significant decreased ferric reducing ability (p<0.001) and thiol groups (p<0.001) in ALS patients compared to controls. When comparing different genotypes of PGC-1α, no relation between Gly482Ser polymorphism and oxidative stress biomarker levels was detected in resting conditions. On the other hand, when considering exercise performance, lactate levels were significantly higher (between p<0.01 and p<0.001) and greater protein oxidative products were found in AA (Ser482Ser) compared to GG (Gly482Gly) and GA (Gly482Ser) ALS patients.Our findings highlight the importance and confirm the involvement of oxidative stress in ALS pathogenesis. Although not associated with 1444 G>A SNP, ALS patients with Gly482Ser allelic variant show increased exercise-related oxidative stress. This thus highlights the possible role of this antioxidant defense transcriptional coactivator in ALS. |
| first_indexed | 2024-04-12T19:37:01Z |
| format | Article |
| id | doaj.art-e92e8f1a1e924323829e4e546adf7700 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-12T19:37:01Z |
| publishDate | 2016-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-e92e8f1a1e924323829e4e546adf77002022-12-22T03:19:11ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022016-04-011010.3389/fncel.2016.00102187163Gly482Ser PGC-1a gene polymorphism and exercise-related oxidative stress in Amyotrophic Lateral Sclerosis patientsAngelique ePasquinelli0Lucia eChico1Livia ePasquali2Costanza eBisordi3Annalisa eLo Gerfo4Monica eFabbrini5Lucia ePetrozzi6Letizia eMarconi7Elena eCaldarazzo Ienco8Michelangelo eMancuso9Gabriele eSiciliano10University of PisaUniversity of PisaUniversity of PisaUniversity of PisaUniversity of PisaUniversity of PisaUniversity of PisaUniversity of PisaUniversity of PisaUniversity of PisaUniversity of PisaThe role of exercise in Amyotrophic Lateral Sclerosis (ALS) pathogenesis is controversial and unclear. Exercise induces a pleiotropic adaptive response in skeletal muscle, largely through the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a transcriptional coactivator that regulates mitochondrial biogenesis and antioxidant defense mechanisms. It has been suggested that a Gly482Ser substitution in PGC-1α has functional relevance in human disorders and in athletic performance. To test this hypothesis, we examined the genotype distribution of PGC-1α Gly482Ser (1444 G>A) in ALS patients to evaluate whether or not the minor serine-encoding allele 482Ser is involved in oxidative stress responses during physical exercise. We genotyped 197 sporadic ALS patients and 197 healthy controls in order to detect differences in allelic frequencies and genotype distribution between the two groups. A total of 74 ALS patients and 65 controls were then comparatively assessed for plasmatic levels of the oxidative stress biomarkers, advanced oxidation protein products, ferric reducing ability and thiol groups. In addition a subgroup of 35 ALS patients were also assessed for total SOD and catalase plasmatic activity. Finally in 28 ALS patients we evaluated the plasmatic curve of the oxidative stress biomarkers and lactate during an incremental exercise test. No significant differences were observed in the genotype distribution and allelic frequency in ALS patients compared to the controls. We found significant increased advanced oxidation protein products (p<0.001) and significant decreased ferric reducing ability (p<0.001) and thiol groups (p<0.001) in ALS patients compared to controls. When comparing different genotypes of PGC-1α, no relation between Gly482Ser polymorphism and oxidative stress biomarker levels was detected in resting conditions. On the other hand, when considering exercise performance, lactate levels were significantly higher (between p<0.01 and p<0.001) and greater protein oxidative products were found in AA (Ser482Ser) compared to GG (Gly482Gly) and GA (Gly482Ser) ALS patients.Our findings highlight the importance and confirm the involvement of oxidative stress in ALS pathogenesis. Although not associated with 1444 G>A SNP, ALS patients with Gly482Ser allelic variant show increased exercise-related oxidative stress. This thus highlights the possible role of this antioxidant defense transcriptional coactivator in ALS.http://journal.frontiersin.org/Journal/10.3389/fncel.2016.00102/fullExerciseOxidative StressPolymorphism, Single NucleotideAmyotrophic lateral sclerosis (ALS)PGC-1α |
| spellingShingle | Angelique ePasquinelli Lucia eChico Livia ePasquali Costanza eBisordi Annalisa eLo Gerfo Monica eFabbrini Lucia ePetrozzi Letizia eMarconi Elena eCaldarazzo Ienco Michelangelo eMancuso Gabriele eSiciliano Gly482Ser PGC-1a gene polymorphism and exercise-related oxidative stress in Amyotrophic Lateral Sclerosis patients Frontiers in Cellular Neuroscience Exercise Oxidative Stress Polymorphism, Single Nucleotide Amyotrophic lateral sclerosis (ALS) PGC-1α |
| title | Gly482Ser PGC-1a gene polymorphism and exercise-related oxidative stress in Amyotrophic Lateral Sclerosis patients |
| title_full | Gly482Ser PGC-1a gene polymorphism and exercise-related oxidative stress in Amyotrophic Lateral Sclerosis patients |
| title_fullStr | Gly482Ser PGC-1a gene polymorphism and exercise-related oxidative stress in Amyotrophic Lateral Sclerosis patients |
| title_full_unstemmed | Gly482Ser PGC-1a gene polymorphism and exercise-related oxidative stress in Amyotrophic Lateral Sclerosis patients |
| title_short | Gly482Ser PGC-1a gene polymorphism and exercise-related oxidative stress in Amyotrophic Lateral Sclerosis patients |
| title_sort | gly482ser pgc 1a gene polymorphism and exercise related oxidative stress in amyotrophic lateral sclerosis patients |
| topic | Exercise Oxidative Stress Polymorphism, Single Nucleotide Amyotrophic lateral sclerosis (ALS) PGC-1α |
| url | http://journal.frontiersin.org/Journal/10.3389/fncel.2016.00102/full |
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