Comparison of post-translational modifications of alpha A-crystallin from normal and hereditary cataract rats

Fujii, Nobutaka; Takeuchi, Noriko; Tezuka, Takafumi; Kuge, Katsunori; Takata, Takumi; Kamei, Akira; Saito, Takeshi

doi:10.1007/s00726-003-0050-8

Cited by 23 publications

(15 citation statements)

References 15 publications

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“…Another reason for this was the possibility that the accelerated aspartic acid racemization rate originated from cataracts in lens of old mammals such as human [23] and rat [24]. The amount of changes of Asp D/L in lens of younger animals was higher than older animals, because the Asp D/L exponential decays in lens of mammals, suggesting that k Asp is more precisely estimated for young animals.…”

Section: Standard Error Of Age Estimated By Aarmentioning

confidence: 99%

Age estimation of Antarctic minke whales Balaenoptera bonaerensis based on aspartic acid racemization technique

Yasunaga¹,

Pastene²,

Bando³

et al. 2017

Fish Sci

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Section: Standard Error Of Age Estimated By Aarmentioning

confidence: 99%

Age estimation of Antarctic minke whales Balaenoptera bonaerensis based on aspartic acid racemization technique

Yasunaga¹,

Pastene²,

Bando³

et al. 2017

Fish Sci

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“…However, to date, the impact of these modifications on the chaperone ability of sHsps to prevent amyloid fibril formation has not been investigated. This area of study is significant since these post-translational modifications occur to a significant extent to the crystallin proteins in the eye lens [12, [127][128][129][130][131][132][133]. There is increasing evidence that cataract may be an amyloid fibril based disease (see below) and, as such, the impact of such modifications on the chaperone ability of α-crystallin to prevent this process is highly relevant.…”

Section: The Effect Of Post-translational Modifications On the Chapermentioning

confidence: 99%

Crystallin proteins and amyloid fibrils

Ecroyd

Carver

2008

Cell. Mol. Life Sci.

220

234

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Improper protein folding (misfolding) can lead to the formation of disordered (amorphous) or ordered (amyloid fibril) aggregates. The major lens protein, alpha-crystallin, is a member of the small heat-shock protein (sHsp) family of intracellular molecular chaperone proteins that prevent protein aggregation. Whilst the chaperone activity of sHsps against amorphously aggregating proteins has been well studied, its action against fibril-forming proteins has received less attention despite the presence of sHsps in deposits found in fibril-associated diseases (e.g. Alzheimer's and Parkinson's). In this review, the literature on the interaction of alpha B-crystallin and other sHsps with fibril-forming proteins is summarized. In particular, the ability of sHsps to prevent fibril formation, their mechanisms of action and the possible in vivo consequences of such associations are discussed. Finally, the fibril-forming propensity of the crystallin proteins and its implications for cataract formation are described along with the potential use of fibrillar crystallin proteins as bionanomaterials. Improper protein folding (misfolding) can lead to the formation of disordered (amorphous) or ordered (amyloid fibril) aggregates. The major lens protein, α-crystallin, is a member of the small heat-shock protein (sHsp) family of intracellular molecular chaperone proteins that prevent protein aggregation. Whilst the chaperone activity of sHsps against amorphously aggregating proteins has been well studied, its action against fibril-forming proteins has received less attention despite the presence of sHsps in deposits found in fibril-associated diseases (e.g. Alzheimer's and Parkinson's). In this review, the literature on the interaction of αB-crystallin and other sHsps with fibril-forming proteins is summarized. In particular, the ability of sHsps to prevent fibril formation, their mechanisms of action and the possible in vivo consequences of such associations are discussed. Finally, the fibril-forming propensity of the crystallin proteins and its implications for cataract formation are described along with the potential use of fibrillar crystallin proteins as bionanomaterials.

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“…It has also been shown that methionines of αA- and αB-crystallins are oxidized in clear middle-aged (45–65) human lenses [20–21]. Importantly, αA-crystallin is found to be oxidized to methionine sulfoxide in rat hereditary cataracts [22] and interestingly, substitution of methionine 68 in αB-crystallin with a less hydrophobic residue (Thr) leads to loss of chaperone activity [23]. These data provide evidence that methionine oxidation plays a key role in cataract formation through loss of α-crystallin chaperone function.…”

Section: Introductionmentioning

confidence: 99%

Methionine sulfoxide reductase A (MsrA) restores α-crystallin chaperone activity lost upon methionine oxidation

Brennan

Lee

Giblin

et al. 2009

Biochimica et Biophysica Acta (BBA) - General Subjects

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Background Lens cataract is associated with protein oxidation and aggregation. Two proteins that cause cataract when deleted from the lens are methionine sulfoxide reductase A (MsrA) that repairs protein methionine sulfoxide (PMSO) oxidized proteins and α-crystallin which is a two subunit (αA and αB) chaperone. Here, we tested whether PMSO formation damages α-crystallin chaperone function and whether MsrA could repair PMSO-α-crystallin. Methods Total α-crystallin was oxidized to PMSO and evaluated by CNBr-cleavage and mass spectrometry. Chaperone activity was measured by light scattering using lysozyme as target. PMSO-α-crystallin was treated with MsrA, and repair was assessed by CNBr cleavage, mass spectrometry and recovery of chaperone function. The levels of α-crystallin-PMSO in the lenses of MsrA-knockout relative to wild-type mice were determined. Results PMSO oxidation of total α-crystallin (met 138 of αA and met 68 of αB) resulted in loss of α-crystallin chaperone activity. MsrA treatment of PMSO-α-crystallin repaired its chaperone activity through reduction of PMSO. Deletion of MsrA in mice resulted in increased levels of PMSO-α-crystallin. Conclusions Methionine oxidation damages α-crystallin chaperone function and MsrA can repair PMSO-α-crystallin restoring its chaperone function. MsrA is required for maintaining the reduced state of α-crystallin methionines in the lens. Significance Methionine oxidation of α-crystallin in combination with loss of MsrA repair causes loss of α-crystallin chaperone function. Since increased PMSO levels and loss of α-crystallin function are hallmarks of cataract, these results provide insight into the mechanisms of cataract development and likely those of other age-related diseases.

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Comparison of post-translational modifications of alpha A-crystallin from normal and hereditary cataract rats

Cited by 23 publications

References 15 publications

Age estimation of Antarctic minke whales Balaenoptera bonaerensis based on aspartic acid racemization technique

Age estimation of Antarctic minke whales Balaenoptera bonaerensis based on aspartic acid racemization technique

Crystallin proteins and amyloid fibrils

Methionine sulfoxide reductase A (MsrA) restores α-crystallin chaperone activity lost upon methionine oxidation

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