Age-related Changes in Bovine α-crystallin and High-molecular-weight Protein

Carver, John A.; Nicholls, K. A.; Aquilina, J. Andrew; Truscott, Roger J.W.

doi:10.1006/exer.1996.0158

Cited by 71 publications

(56 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…35,43,44 a H -Crystallin has been considered to be an intermediate between the soluble and insoluble fractions, which contained more bound b-and g-crystallins than a L -crystallin. A decrease in a L -crystallin with an increase in a H -crystallin in selenite lens would lead to a decrease in active a-crystallin to provide protection.…”

Section: Discussionmentioning

confidence: 99%

Decreased chaperone activity of α-crystallin in selenite cataract may result from selenite-induced aggregation

Yan

Harding

Hui

et al. 2003

Eye

View full text Add to dashboard Cite

Purpose To investigate the role of chaperone activity of a-crystallin in selenite-induced cataract formation. Methods Selenite cataract was induced in Sprague-Dawley rats by five subcutaneous injections of sodium selenite over a 20-day period starting at 8-10 days postpartum. a-Crystallin was separated from the rat lenses by size-exclusion chromatography. Bovine a L -crystallin and b L -crystallin were isolated for studies in vitro, and for the chaperone assays. The protective effects of both a H -and a L -crystallin were measured spectrophotometrically in four different assay procedures including the thermally induced aggregation of catalase and b L -crystallin, and the fructation-and heat-induced inactivation of catalase. The bovine a L -crystallin was incubated with different concentrations of sodium selenite for 72 h and then its chaperone activity against heat-induced b L -crystallin aggregation was assayed. The aggregation of selenite-treated a L -crystallin was analysed by molecular sieve high-performance liquid chromatography (HPLC). Results The protection of a H -crystallin was less than that of a L -crystallin in both normal and cataractous lenses. The chaperone activities of both a H -and a L -crystallin in selenite cataract were decreased compared with normal lenses. The protection provided by both a H -crystallin and a L -crystallin against the thermal aggregation of catalase was much greater than their protection against thermally and chemically induced inactivation. HPLC analysis demonstrated aggregation of a-crystallin by sodium selenite after 24 h incubation in a dose-dependent fashion. ConclusionThe chaperone activity of a-crystallin presented parallel patterns of activity with different methods, further supporting the view that the different assays measure essentially the same property. The decreased chaperone activity of a-crystallin in selenite cataract may result from seleniteinduced aggregation.

show abstract

Section: Discussionmentioning

confidence: 99%

Decreased chaperone activity of α-crystallin in selenite cataract may result from selenite-induced aggregation

Yan

Harding

Hui

et al. 2003

Eye

View full text Add to dashboard Cite

show abstract

“…Crystallin proteins were purified from bovine lenses as described previously by standard methods via size exclusion chromatography from cows of less than two years in age (19). SDS-polyacrylamide gel electrophoresis was used to confirm the purity of ␣-, ␤-, and ␥-crystallins.…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, the chaperone ability of ␣-crystallin is reduced significantly at lower pH values (47,48), which would favor enhanced protein precipitation including that arising from fibril formation by the other crystallins. There is also less chaperone-active ␣-crystallin present in the aging lens (4,19), which would lead to a reduction in its ability to deal with crystallin aggregation, and thereby potentially open up an opportunity for fibril formation indirectly.…”

Section: Fig 4 Cr Assaymentioning

confidence: 99%

Amyloid Fibril Formation by Lens Crystallin Proteins and Its Implications for Cataract Formation

Meehan

Berry

Luisi

et al. 2004

Journal of Biological Chemistry

Self Cite

177

187

View full text Add to dashboard Cite

The ␣-, ␤-, and ␥-crystallins are the major structural proteins within the eye lens and are responsible for its exceptional stability and transparency. Under mildly denaturing conditions, all three types of bovine crystallin assemble into fibrillar structures in vitro. Characterization by transmission electron microscopy, dye binding assays, and x-ray fiber diffraction shows that these species have all of the characteristics of fibrils associated with the family of amyloid diseases. Moreover, the full-length proteins are incorporated into the fibrils, (i.e. no protein cleavage is required for these species to form), although for the ␥-crystallins some fragmentation occurs under the conditions employed in this study. Our findings indicate that the inherent stability of the ␤-sheet supramolecular structure adopted by the crystallins in the eye lens and the chaperone ability of ␣-crystallin must be crucial for preventing fibril formation in vivo. The crystallins are very stable proteins but undergo extensive post-translational modification with age that leads to their destabilization. The ability of the crystallins to convert into fibrils under destabilizing conditions suggests that this process could contribute to the development of cataract with aging.

show abstract

“…Various types of cellular stress, such as heat, oxidation and increased intracellular calcium levels, stimulate the phosphorylation of sHsps [111]. With regard to αB-crystallin, phosphorylation is mediated by at least two distinct mitogenactivated protein kinase enzymes, mitogen-activated protein kinases associated protein kinase2 (MAPKAPK2) and p42/p44 MAPK [111,112,115,116] and, in the lens, phosphorylation increases with age [117,118]. However, even in the young lens, αB-crystallin is extensively phosphorylated [113,118].…”

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

confidence: 99%

“…With regard to αB-crystallin, phosphorylation is mediated by at least two distinct mitogenactivated protein kinase enzymes, mitogen-activated protein kinases associated protein kinase2 (MAPKAPK2) and p42/p44 MAPK [111,112,115,116] and, in the lens, phosphorylation increases with age [117,118]. However, even in the young lens, αB-crystallin is extensively phosphorylated [113,118]. All three sites of serine phosphorylation of Hsp27 are mediated by MAPKAP kinases [119,120].…”

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

confidence: 99%

Crystallin proteins and amyloid fibrils

Ecroyd

Carver

2008

Cell. Mol. Life Sci.

Self Cite

221

234

View full text Add to dashboard Cite

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.

show abstract

Age-related Changes in Bovine α-crystallin and High-molecular-weight Protein

Cited by 71 publications

References 0 publications

Decreased chaperone activity of α-crystallin in selenite cataract may result from selenite-induced aggregation

Decreased chaperone activity of α-crystallin in selenite cataract may result from selenite-induced aggregation

Amyloid Fibril Formation by Lens Crystallin Proteins and Its Implications for Cataract Formation

Crystallin proteins and amyloid fibrils

Contact Info

Product

Resources

About