200 KD neurofilament protein binds AL, CU and ZN

Pierson, Keith B.; Evenson, Merle A.

doi:10.1016/s0006-291x(88)80080-9

Cited by 30 publications

(17 citation statements)

References 14 publications

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“…x iO~M~) (Dawson et al, 1989). Neurofilament proteins are present in high abundance along with SOD in motor neurons and are known to bind metals (Pierson and Evenson, 1988;Shen et al, 1994), as is metallothionein (Shaw et al, 1991). Therefore, we compared the relative abilities of NF-L and apometallothionein II to compete for zinc present as Zn-PAR 2.…”

Section: Resultsmentioning

confidence: 99%

Decreased Zinc Affinity of Amyotrophic Lateral Sclerosis‐Associated Superoxide Dismutase Mutants Leads to Enhanced Catalysis of Tyrosine Nitration by Peroxynitrite

Crow¹,

Sampson²,

Zhuang³

et al. 1997

Journal of Neurochemistry

451

344

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Mutations to Cu/Zn superoxide dismutase (SOD) linked to familial amyotrophic lateral sclerosis (ALS) enhance an unknown toxic reaction that leads to the selective degeneration of motor neurons. However, the question of how >50 different missense mutations produce a common toxic phenotype remains perplexing. We found that the zinc affinity of four ALS‐associated SOD mutants was decreased up to 30‐fold compared to wild‐type SOD but that both mutants and wild‐type SOD retained copper with similar affinity. Neurofilament‐L (NF‐L), one of the most abundant proteins in motor neurons, bound multiple zinc atoms with sufficient affinity to potentially remove zinc from both wild‐type and mutant SOD while having a lower affinity for copper. The loss of zinc from wild‐type SOD approximately doubled its efficiency for catalyzing peroxynitrite‐mediated tyrosine nitration, suggesting that one gained function by SOD in ALS may be an indirect consequence of zinc loss. Nitration of protein‐bound tyrosines is a permanent modification that can adversely affect protein function. Thus, the toxicity of ALS‐associated SOD mutants may be related to enhanced catalysis of protein nitration subsequent to zinc loss. By acting as a high‐capacity zinc sink, NF‐L could foster the formation of zinc‐deficient SOD within motor neurons.

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Section: Resultsmentioning

confidence: 99%

Decreased Zinc Affinity of Amyotrophic Lateral Sclerosis‐Associated Superoxide Dismutase Mutants Leads to Enhanced Catalysis of Tyrosine Nitration by Peroxynitrite

Crow¹,

Sampson²,

Zhuang³

et al. 1997

Journal of Neurochemistry

451

344

View full text Add to dashboard Cite

show abstract

“…Neurofilament proteins show a high affinity and binding capacity for zinc (Pierson and Evenson, 1988), and NF-L can specifically extract zinc from wild-type and mutant forms of SOD1. NF-L may form a high affinity and abundant site favoring the accumulation of zinc-deficient SOD1 (Crow et al , 1997a).…”

Section: Als and Protein Nitrationmentioning

confidence: 99%

Nitric Oxide-Mediated Oxidative Damage and the Progressive Demise of Motor Neurons in ALS

et al. 2012

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“…The nature of association of aluminum with NFPs exhibits a degree of specificity because neither the trivalent cation Fe3+ nor the divalent cation Ca2+ or Mg2+ altered subunit electrophoretic mobility, nor could they prevent or reverse the effect of aluminum on NFPs. In addition to t5e potential association of aluminum with incorporated phosphate groups (see above), A13+ is capable of binding to phosphatase-insensitive sites on neurofilament polypeptides (Pierson and Evenson, 1988) that normally bind Ca2+ (Lefebvre and Mushynski, 1988). Displacement of calcium by aluminum may be one factor contributing to the resistance of aluminum-treated NFPs to calcium-dependent proteolysis .…”

Section: Figmentioning

confidence: 99%

Aluminum Alters the Electrophoretic Properties of Neurofilament Proteins: Role of Phosphorylation State

Shea

Beermann

Nixon

1992

Journal of Neurochemistry

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Exposure of each of the three neurofilament proteins (NFPs) to AlCl3 resulted in their failure to migrate into sodium dodecyl sulfate (SDS)-containing gels. This effect was dependent on length of incubation (minimum, 2 h) and AlCl3 concentrations (minimum, 50 microM) and was not reversed by 20% SDS, 6 M urea, freeze-thawing, boiling, or extensive dialysis. The migration of vimentin and glial fibrillary acidic protein was not affected by AlCl3. The high-molecular-weight neurofilament subunit (NF-H) entered SDS-containing gels after exposure to aluminum lactate but migrated aberrantly as a long high-molecular-weight streak. Migration of the 160-kDa alpha-chymotryptic cleavage product of NF-H, which contains the higher phosphorylated tail domain, was also prevented from migrating into SDS-containing gels by AlCl3. Dephosphorylation of NF-H and the middle-molecular-weight neurofilament subunit (NF-M) eliminated these effects on gel migration. EDTA, EGTA, MgCl2, CaCl2, or FeCl3 had no effect on NF-H or NF-M migration; furthermore, preincubation with, or simultaneous exposure to, CaCl2 or FeCl3 did not alter the effect of AlCl3. One interpretation of these results is that Al3+ interacts with phosphate groups on extensively phosphorylated C-terminal sidearms of NFPs, resulting in intermolecular cross-linking. These findings demonstrate a direct effect of aluminum on NFPs and provide a possible mechanism for neurofilament accumulation in perikarya during aluminum intoxication.

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200 KD neurofilament protein binds AL, CU and ZN

Cited by 30 publications

References 14 publications

Decreased Zinc Affinity of Amyotrophic Lateral Sclerosis‐Associated Superoxide Dismutase Mutants Leads to Enhanced Catalysis of Tyrosine Nitration by Peroxynitrite

Decreased Zinc Affinity of Amyotrophic Lateral Sclerosis‐Associated Superoxide Dismutase Mutants Leads to Enhanced Catalysis of Tyrosine Nitration by Peroxynitrite

Nitric Oxide-Mediated Oxidative Damage and the Progressive Demise of Motor Neurons in ALS

Aluminum Alters the Electrophoretic Properties of Neurofilament Proteins: Role of Phosphorylation State

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