Superoxide dismutase mutations of familial amyotrophic lateral sclerosis and the oxidative inactivation of calcineurin

Völkel, Helge; Scholz, Maike; Link, Johannes; Selzle, Martin; Werner, Peter; Tunnemann, Ralf; Jung, G.; Ludolph, Albert C.; Reuter, Alexander

doi:10.1016/s0014-5793(01)02730-2

Cited by 17 publications

(16 citation statements)

References 25 publications

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“…That calcineurin was found to interact with SOD was not surprising considering there is an interaction between neuronal Cu, Zn SOD, and calcineurin, such as in familial amyotrophic lateral sclerosis (fALS). In this disease state, a variant of SOD1 is typical and is seemingly accompanied by a decrease in calcineurin activity22–24 in contrast to the apparent protection afforded calcineurin by the wild type SOD1 in vitro 25. SOD1 is not a mitochondrial protein, but SOD2 is only found in the mitochondria.…”

Section: Resultsmentioning

confidence: 99%

Association of calcineurin with mitochondrial proteins

Tokheim

Martin

2006

Proteins

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Using mouse hearts from Swiss Webster mice, calcineurin was immunoprecipitated using commercially available anti-calcineurin antibody and the resulting complex analyzed by using sodium dodecyl sulfate-gel electrophoresis with silver staining. Distinct proteins were observed and subjected to in situ trypsin digestion followed by extraction of the resulting peptides. Peptides from each protein band were loaded onto a target for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and analyzed. The resulting peptide mass spectrum was compared with the Mascot and Protein Prospector databases and resulted in the specific identification of heart mitochondrial proteins, specifically Mn-superoxide dismutase (SOD), aconitase (ACN), and malate dehydrogenase (MDH). Each of the three mitochondrial enzymes was identified with approximately 15-25% sequence coverage and all with statistical significance (P < 0.05) according to the Mascot database search engine. Tandem mass spectrometry analysis of the peptide fragmentation spectra confirmed the identification of these protein partners and also yielded the identification of mitochondrial isocitrate dehydrogenase (ICDH) as another protein in the immunoprecipitated complex. Using antibody preparations against Mn-SOD, ACN, and ICDH showed the presence of calcineurin and each of the three proteins in the immunoprecipitated complex by Western slot blotting. The activity of ACN, but not MDH or ICDH, was enhanced after incubation with calcineurin indicating one possible regulatory function for the complex. The mitochondrial forms of Mn-SOD, ACN, MDH, and ICDH were identified as partner proteins of calcineurin with all the proteins present in a single multiprotein complex.

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Section: Resultsmentioning

confidence: 99%

Association of calcineurin with mitochondrial proteins

Tokheim

Martin

2006

Proteins

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“…The wild-type SOD was shown to protect calcineurin from inactivation by reactive oxygen species. The degree of protection against inactivation of calcineurin by different SOD mutants correlates with the severity of the ALS phenotype, suggesting a potential role for calcineurin-SOD1 interaction in the etiology of fALS [125].…”

Section: Calmodulin and The Ca 2+ /Calmodulin-dependent Protein Kinasesmentioning

confidence: 99%

Calcium-dependent protein folding in amyotrophic lateral sclerosis

2013

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“…The final example involves a private CNVR on chromosome 13 (52.0-52.1 Mb, Table 2) which includes the superoxide dismutase gene (SOD1; accession NM_174615). Mutations in SOD1 are responsible for degenerative myelopathy in dogs (Awano et al, 2009) and humans (Volkel et al, 2001) and a recent study suggests that it is under selection in cattle and possibly associated with the poll gene (Li et al, 2010).…”

Section: Gene Content Of Cnv Regionsmentioning

confidence: 99%