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Oxidative Stress in Caenorhabditis elegans: Protective Effects of Spartin.

Truong T, Karlinski ZA, O'Hara C, Cabe M, Kim H, Bakowska JC - PLoS ONE (2015)

Bottom Line: These results suggest an age-dependent decline in motor function in mutant animals.In the behavioral assays, spg-20 mutant animals showed a significant decrease in both crawling speed and thrashing frequency compared with wild-type animals.These data suggest that the protein F57B10.9/SPG-20 might have a protective role against oxidative stress.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Pharmacology and Therapeutics, Loyola University Chicago, Maywood, Illinois, United States of America.

ABSTRACT
Troyer syndrome is caused by a mutation in the SPG20 gene, which results in complete loss of expression of the protein spartin. We generated a genetic model of Troyer syndrome in worms to explore the locomotor consequences of a mutation of the Caenorhabditis elegans SPG20 orthologue, F57B10.9, also known as spg-20. Spg-20 mutants showed decreased length, crawling speed, and thrashing frequency, and had a shorter lifespan than wild-type animals. These results suggest an age-dependent decline in motor function in mutant animals. The drug paraquat was used to induce oxidative stress for 4 days in the animals. We measured survival rate and examined locomotion by measuring crawling speed and thrashing frequency. After 4 days of paraquat exposure, 77% of wild-type animals survived, but only 38% of spg-20 mutant animals survived. Conversely, animals overexpressing spg-20 had a survival rate of 95%. We also tested lifespan after a 1 hour exposure to sodium azide. After a 24 hour recovery period, 87% of wild type animals survived, 57% of spg-20 mutant animals survived, and 82% of animals overexpressing spg-20 survived. In the behavioral assays, spg-20 mutant animals showed a significant decrease in both crawling speed and thrashing frequency compared with wild-type animals. Importantly, the locomotor phenotype for both crawling and thrashing was rescued in animals overexpressing spg-20. The animals overexpressing spg-20 had crawling speeds and thrashing frequencies similar to those of wild-type animals. These data suggest that the protein F57B10.9/SPG-20 might have a protective role against oxidative stress.

No MeSH data available.


Related in: MedlinePlus

Protein F57B10.9 in C. elegans is the orthologue of SPG20 in H. sapiens.(A) Protein sequence alignment using Clustal omega of F57B10.9 and SPG20. These sequences share 23% identity and 65% similarity. Conserved amino acids are marked in grey, and identical amino acids are marked in black. (B) F57B10.9 has one predicted transcript, and the tm5514 deletion mutation spans exons 1 through 6.
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pone.0130455.g001: Protein F57B10.9 in C. elegans is the orthologue of SPG20 in H. sapiens.(A) Protein sequence alignment using Clustal omega of F57B10.9 and SPG20. These sequences share 23% identity and 65% similarity. Conserved amino acids are marked in grey, and identical amino acids are marked in black. (B) F57B10.9 has one predicted transcript, and the tm5514 deletion mutation spans exons 1 through 6.

Mentions: In H. sapiens, the SPG20 gene that codes for spartin protein has a mutation that leads to loss of function and neurodegeneration of the cortical spinal projections. To better understand the pathogenesis and the possible behavioral changes resulting from the loss of spartin, we used the model organism, C. elegans, and characterized the C. elegans ortholog of SPG20 in H. sapiens, the F57B10.9 gene, also known as spg-20. We examined the tm5514 deletion, which results in a allele of spg-20. The spartin protein in C. elegans shares 23% identity and 65% similarity with SPG20 in H. sapiens (Blast e-value 3x10-23). Spartin contains three evolutionarily conserved domains, including the MIT, the UBR, and the PSD [7–8]. MIT spans amino acids 14–90 in F57B10.9 (a protein product of its cognate gene) and 16–95 in SPG20 and shares 20% identity and 62% similarity. UBR spans amino acids 270–367 in SPG20 and shares 29% identity and 60% similarity between F57B10.9 and SPG20. PSD spans amino acids 261–439 in F57B10.9 and 427–613 in SPG20 and shares 25% identity and 77% similarity (Fig 1A).


Oxidative Stress in Caenorhabditis elegans: Protective Effects of Spartin.

Truong T, Karlinski ZA, O'Hara C, Cabe M, Kim H, Bakowska JC - PLoS ONE (2015)

Protein F57B10.9 in C. elegans is the orthologue of SPG20 in H. sapiens.(A) Protein sequence alignment using Clustal omega of F57B10.9 and SPG20. These sequences share 23% identity and 65% similarity. Conserved amino acids are marked in grey, and identical amino acids are marked in black. (B) F57B10.9 has one predicted transcript, and the tm5514 deletion mutation spans exons 1 through 6.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4482654&req=5

pone.0130455.g001: Protein F57B10.9 in C. elegans is the orthologue of SPG20 in H. sapiens.(A) Protein sequence alignment using Clustal omega of F57B10.9 and SPG20. These sequences share 23% identity and 65% similarity. Conserved amino acids are marked in grey, and identical amino acids are marked in black. (B) F57B10.9 has one predicted transcript, and the tm5514 deletion mutation spans exons 1 through 6.
Mentions: In H. sapiens, the SPG20 gene that codes for spartin protein has a mutation that leads to loss of function and neurodegeneration of the cortical spinal projections. To better understand the pathogenesis and the possible behavioral changes resulting from the loss of spartin, we used the model organism, C. elegans, and characterized the C. elegans ortholog of SPG20 in H. sapiens, the F57B10.9 gene, also known as spg-20. We examined the tm5514 deletion, which results in a allele of spg-20. The spartin protein in C. elegans shares 23% identity and 65% similarity with SPG20 in H. sapiens (Blast e-value 3x10-23). Spartin contains three evolutionarily conserved domains, including the MIT, the UBR, and the PSD [7–8]. MIT spans amino acids 14–90 in F57B10.9 (a protein product of its cognate gene) and 16–95 in SPG20 and shares 20% identity and 62% similarity. UBR spans amino acids 270–367 in SPG20 and shares 29% identity and 60% similarity between F57B10.9 and SPG20. PSD spans amino acids 261–439 in F57B10.9 and 427–613 in SPG20 and shares 25% identity and 77% similarity (Fig 1A).

Bottom Line: These results suggest an age-dependent decline in motor function in mutant animals.In the behavioral assays, spg-20 mutant animals showed a significant decrease in both crawling speed and thrashing frequency compared with wild-type animals.These data suggest that the protein F57B10.9/SPG-20 might have a protective role against oxidative stress.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Pharmacology and Therapeutics, Loyola University Chicago, Maywood, Illinois, United States of America.

ABSTRACT
Troyer syndrome is caused by a mutation in the SPG20 gene, which results in complete loss of expression of the protein spartin. We generated a genetic model of Troyer syndrome in worms to explore the locomotor consequences of a mutation of the Caenorhabditis elegans SPG20 orthologue, F57B10.9, also known as spg-20. Spg-20 mutants showed decreased length, crawling speed, and thrashing frequency, and had a shorter lifespan than wild-type animals. These results suggest an age-dependent decline in motor function in mutant animals. The drug paraquat was used to induce oxidative stress for 4 days in the animals. We measured survival rate and examined locomotion by measuring crawling speed and thrashing frequency. After 4 days of paraquat exposure, 77% of wild-type animals survived, but only 38% of spg-20 mutant animals survived. Conversely, animals overexpressing spg-20 had a survival rate of 95%. We also tested lifespan after a 1 hour exposure to sodium azide. After a 24 hour recovery period, 87% of wild type animals survived, 57% of spg-20 mutant animals survived, and 82% of animals overexpressing spg-20 survived. In the behavioral assays, spg-20 mutant animals showed a significant decrease in both crawling speed and thrashing frequency compared with wild-type animals. Importantly, the locomotor phenotype for both crawling and thrashing was rescued in animals overexpressing spg-20. The animals overexpressing spg-20 had crawling speeds and thrashing frequencies similar to those of wild-type animals. These data suggest that the protein F57B10.9/SPG-20 might have a protective role against oxidative stress.

No MeSH data available.


Related in: MedlinePlus