Î±-Crystallin as a molecular chaperone

Derham, Barry K.; Harding, John J.

doi:10.1016/s1350-9462(98)00030-5

Cited by 279 publications

(246 citation statements)

References 279 publications

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“…As an sHSP, αBC is known to play a role in the cellular defense against improperly degraded, accumulated and toxic proteins [19,20]. αBC specifically recognizes and stabilizes proteins that have a propensity to aggregate and precipitate [19,20].…”

Section: Discussionmentioning

confidence: 99%

“…αBC specifically recognizes and stabilizes proteins that have a propensity to aggregate and precipitate [19,20]. In Alzheimer brain, αBC binds to AβPP [26], and αBC mRNA is increased (referenced in [26]).…”

Section: Discussionmentioning

confidence: 99%

“…Since increased expression of αBC can occur under various stressful conditions [reviewed in 19,20], we hypothesize that in morphologically "undamaged" s-IBM muscle fibers, αBC is induced as a secondary reaction in response to the early increase in them of "morphologically invisible" soluble Aβ-oligomers (not in aggregates). To test this hypothesis, we studied αBC in cultured human muscle fibers shortly after AβPP-overexpression in them, before typical structural abnormalities developed.…”

Section: Introductionmentioning

confidence: 99%

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AβPP-overexpression and proteasome inhibition increase αB-crystallin in cultured human muscle: Relevance to inclusion-body myositis

Wójcik

Engel

McFerrin

et al. 2006

Neuromuscular Disorders

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Amyloid-β precursor protein (AβPP) and its fragment amyloid-β (Aβ) are increased in s-IBM muscle fibers and appear to play an important role in the pathogenic cascade. αB-crystallin (αBC) was shown immunohistochemically to be accumulated in s-IBM muscle fibers, but the stressor(s) influencing αBC accumulation was not identified. We now demonstrate, using our experimental IBM model based on genetic overexpression of AβPP into normal culture human muscle fibers, that: 1) AβPP overexpression increased αBC 3.7-fold (p= 0.025); 2) additional inhibition of proteasome with epoxomicin increased αBC 7-fold (p=0.002); and 3) αBC physically associated with AβPP and Aβ oligomers. We also show that in biopsied s-IBM muscle fibers, αBC was similarly increased 3-fold (p=0.025) and physically associated with AβPP and Aβ oligomers. We propose that increased AβPP is a stressor increasing αBC expression in s-IBM muscle fibers. Determining the consequences of αBC association with Aβ oligomers could have clinical therapeutic relevance.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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AβPP-overexpression and proteasome inhibition increase αB-crystallin in cultured human muscle: Relevance to inclusion-body myositis

Wójcik

Engel

McFerrin

et al. 2006

Neuromuscular Disorders

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“…Crystallins are members of the small heat shock protein (sHSP) family (Derham and Harding, 1999). α-Crystallins have been studied extensively in the lens for their chaperone function, but it is now generally accepted that α-crystallins have additional different non-lens roles (Bhat, 2004;Andley, 2007) and are expressed in multiple tissues (Srinivasan et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Exacerbation of retinal degeneration in the absence of alpha crystallins in an in vivo model of chemically induced hypoxia

Yaung

Kannan

Wawrousek

et al. 2008

Experimental Eye Research

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This study evaluated the role of crystallins in retinal degeneration induced by chemical hypoxia. Wild type, αA-crystallin (−/−), and αB-crystallin (−/−) mice received intravitreal injection of 12 nmol (low dose), 33 nmol (intermediate dose) or 60 nmol (high dose) cobalt chloride (CoCl 2 ). Hematoxylin and eosin and TdT-mediated dUTP nick-end labeling (TUNEL) stains were performed after 24 hours, 96 hours, and 1 week post-injection, while immunofluorescent stains for αA-and αB-crystallin were performed 1 week post-injection. The in vitro effects of CoCl 2 on αB-crystallin expression in ARPE-19 cells were determined by real time RT-PCR, Western blot, and confocal microscopy and studies evaluating subcellular distribution of αB-crystallin in the mitochondria and cytosol were also performed. Histologic studies revealed progressive retinal degeneration with CoCl 2 injection in wild type mice. Retinas of CoCl 2 injected mice showed transient increased expression of HIF-1α which was maximal 24 hours after injection. Intermediate dose CoCl 2 injection was associated with increased retinal immunofluorescence for both αA-and αB-crystallin; however, after high dose injection, increased retinal degeneration was associated with decreased levels of crystallin expression. Injection of CoCl 2 at either intermediate or high dose in αA-crystallin (−/−) and αB-crystallin (−/−) mice resulted in much more severe retinal degeneration compared to wild type eyes. A decrease in ARPE-19 total and cytosolic αB-crystallin expression with increasing CoCl2 treatment and an increase in mitochondrial αB-crystallin were found. We conclude that lack of α-crystallins accentuates retinal degeneration in chemically-induced hypoxia in vivo.

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“…23,24 Different assays for chaperone function of a-crystallin have been developed including heat-and UV-induced protein aggregation, sugar, and steroid inactivation of enzymes. 23, 25 Kelley et al 20 showed that the chaperone activity of a-crystallin from the nucleus of rat lenses was diminished in selenite cataract, but their only chaperone assay was a b L -crystallin aggregation assay at 641C, far from physiological temperatures. Assays at physiological temperature are to be preferred.…”

Section: Introductionmentioning

confidence: 99%

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

Yan

Harding

Hui

et al. 2003

Eye

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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.

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Î±-Crystallin as a molecular chaperone

Cited by 279 publications

References 279 publications

AβPP-overexpression and proteasome inhibition increase αB-crystallin in cultured human muscle: Relevance to inclusion-body myositis

AβPP-overexpression and proteasome inhibition increase αB-crystallin in cultured human muscle: Relevance to inclusion-body myositis

Exacerbation of retinal degeneration in the absence of alpha crystallins in an in vivo model of chemically induced hypoxia

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

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