Interactions between Small Heat Shock Protein α-Crystallin and Galectin-Related Interfiber Protein (GRIFIN) in the Ocular Lens

Barton, Kelly A.; Hsu, Chao‐Yu; Petrash, J. Mark

doi:10.1021/bi802203a

Cited by 27 publications

(17 citation statements)

References 47 publications

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“…Several in vitro studies suggest that α-crystallin activity does not require ATP hydrolysis and therefore, α-crystallin becomes particularly significant under stress conditions when the level of ATP is very low (Horwitz, 1992). However, ATP effects have been reported by others, primarily with α-crystallin (Barton et al, 2009; Biswas and Das, 2004; Muchowski and Clark 1998; Wang and Spector, 2000). The identification of β4-β8 groove as the ATP interactive region in αB-crystallin, is in contrast to the existing paradigm that classifies sHSPs as ATP-independent chaperones (Dutta et al, 2010; Ghosh et al, 2006).…”

Section: Function and Properties Of α-Crystallinmentioning

confidence: 94%

“…The multiple β-strands of the β-sheet domain of αcrystallin have been suggested as one of the sites of protein–protein interactions (Hoskins et al, 2006). In addition to stabilizing different structurally compromised proteins during multiple pathological conditions, α-crystallins have been found to interact with several other proteins such as β-crystallins, α-crystallin, actin filaments, vimentin, CP49, filensin, intermediate filaments, VEGF, HSP27, galectin-related interfiber protein, apoptotic mediators, mitochondrial proteins and nuclear proteins (Barton et al, 2009; FitzGerald et al 1991; Ghosh et al, 2007a; Nicholl and Quinlan 1994; Singh et al 2007). A detailed list of α-crystallin interacting partners based on functional categories is presented in Table 1.…”

Section: Function and Properties Of α-Crystallinmentioning

confidence: 99%

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Novel roles for α-crystallins in retinal function and disease

Kannan

Sreekumar

Hinton

2012

Progress in Retinal and Eye Research

111

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α-Crystallins are key members of the superfamily of small heat shock proteins that have been studied in detail in the ocular lens. Recently, novel functions for α-crystallins have been identified in the retina and in the retinal pigmented epithelium (RPE). αB-Crystallin has been localized to multiple compartments and organelles including mitochondria, golgi apparatus, endoplasmic reticulum and nucleus. α-Crystallins are regulated by oxidative and endoplasmic reticulum stress, and inhibit apoptosis-induced cell death. α-Crystallins interact with a large number of proteins that include other crystallins, and apoptotic, cytoskeletal, inflammatory, signaling, angiogenic, and growth factor molecules. Studies with RPE from αB-crystallin deficient mice have shown that αB-crystallin supports retinal and choroidal angiogenesis through its interaction with vascular endothelial growth factor. αB-Crystallin has also been shown to have novel functions in the extracellular space. In RPE, αB-crystallin is released from the apical surface in exosomes where it accumulates in the interphotoreceptor matrix and may function to protect neighboring cells. In other systems administration of exogenous recombinant αB-crystallin has been shown to be anti-inflammatory. Another newly described function of αB-crystallin is its ability to inhibit β-amyloid fibril formation. α-Crystallin mini-chaperone peptides have been identified that elicit anti-apoptotic function in addition to being efficient chaperones. Generation of liposomal particles and other modes of nanoencapsulation of these minipeptides could offer great therapeutic advantage in ocular delivery for a wide variety of retinal degenerative, inflammatory and vascular diseases including age related macular degeneration and diabetic retinopathy.

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Section: Function and Properties Of α-Crystallinmentioning

confidence: 94%

Section: Function and Properties Of α-Crystallinmentioning

confidence: 99%

Novel roles for α-crystallins in retinal function and disease

Kannan

Sreekumar

Hinton

2012

Progress in Retinal and Eye Research

111

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“…[281][282][283] The healthy human lens 284 also expresses galectin-3, and a galectin-like molecule called GRIFIN (galectin-related inter-fiber protein). 285,286 In depth proteomic analysis of normal human CB tissue-which participates in aqueous humor production and aqueous humor outflow through the unconventional pathway-has revealed expression of galectin-1. 287 Additionally, there is now evidence that suggests that galectin-3 may play a role in neuroprotection against glaucomatous damage.…”

Section: Figmentioning

confidence: 99%

Matricellular Proteins in the Trabecular Meshwork: Review and Update

Chatterjee

Villarreal

Rhee

2014

Journal of Ocular Pharmacology and Therapeutics

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Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide, and intraocular pressure (IOP) is an important modifiable risk factor. IOP is a function of aqueous humor production and aqueous humor outflow, and it is thought that prolonged IOP elevation leads to optic nerve damage over time. Within the trabecular meshwork (TM), the eye's primary drainage system for aqueous humor, matricellular proteins generally allow cells to modulate their attachments with and alter the characteristics of their surrounding extracellular matrix (ECM). It is now well established that ECM turnover in the TM affects outflow facility, and matricellular proteins are emerging as significant players in IOP regulation. The formalized study of matricellular proteins in TM has gained increased attention. Secreted protein acidic and rich in cysteine (SPARC), myocilin, connective tissue growth factor (CTGF), and thrombospondin-1 and -2 (TSP-1 and -2) have been localized to the TM, and a growing body of evidence suggests that these matricellular proteins play an important role in IOP regulation and possibly the pathophysiology of POAG. As evidence continues to emerge, these proteins are now seen as potential therapeutic targets. Further study is warranted to assess their utility in treating glaucoma in humans.

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“…Our expression analysis nominated two genes, Grifin and Chst12 (Table 2), as the top candidate genes for the vascular differences because these genes were differentially expressed in the same direction under both normotensive and hypertensive conditions. Grifin is a galectin-related extracellular matrix protein that is highly expressed in the lens and may be structurally important for lens development (2,34). Grifin is also expressed in vascular smooth muscle cells (4), but its role(s) in vascular remodeling and dysfunction have not been elucidated.…”

Section: Discussionmentioning

confidence: 99%

Vascular dysfunction precedes hypertension associated with a blood pressure locus on rat chromosome 12

Prisco

Priestley

Weinberg

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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dysfunction precedes hypertension associated with a blood pressure locus on rat chromosome 12. Am J Physiol Heart Circ Physiol 307: H1103-H1110, 2014. First published August 22, 2014; doi:10.1152/ajpheart.00464.2014.-We previously isolated a 6.1-Mb region of SS/Mcwi (Dahl salt-sensitive) rat chromosome 12 (13.4 -19.5 Mb) that significantly elevated blood pressure (BP) (⌬ϩ34 mmHg, P Ͻ 0.001) compared with the SS-12 BN consomic control. In the present study, we examined the role of vascular dysfunction and remodeling in hypertension risk associated with the 6.1-Mb (13.4 -19.5 Mb) locus on rat chromosome 12 by reducing dietary salt, which lowered BP levels so that there were no substantial differences in BP between strains. Consequently, any observed differences in the vasculature were considered BP-independent. We also reduced the candidate region from 6.1 Mb with 133 genes to 2 Mb with 23 genes by congenic mapping. Both the 2 Mb and 6.1 Mb congenic intervals were associated with hypercontractility and decreased elasticity of resistance vasculature prior to elevations of BP, suggesting that the vascular remodeling and dysfunction likely contribute to the pathogenesis of hypertension in these congenic models. Of the 23 genes within the narrowed congenic interval, 12 were differentially expressed between the resistance vasculature of the 2 Mb congenic and SS-12 BN consomic strains. Among these, Grifin was consistently upregulated 2.7 Ϯ 0.6-fold (P Ͻ 0.05) and 2.0 Ϯ 0.3-fold (P Ͻ 0.01), and Chst12 was consistently downregulated Ϫ2.8 Ϯ 0.3-fold (P Ͻ 0.01) and Ϫ4.4 Ϯ 0.4-fold (P Ͻ 0.00001) in the 2 Mb congenic compared with SS-12 BN consomic under normotensive and hypertensive conditions, respectively. A syntenic region on human chromosome 7 has also been associated with BP regulation, suggesting that identification of the genetic mechanism(s) underlying cardiovascular phenotypes in this congenic strain will likely be translated to a better understanding of human hypertension.

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Interactions between Small Heat Shock Protein α-Crystallin and Galectin-Related Interfiber Protein (GRIFIN) in the Ocular Lens

Cited by 27 publications

References 47 publications

Novel roles for α-crystallins in retinal function and disease

Novel roles for α-crystallins in retinal function and disease

Matricellular Proteins in the Trabecular Meshwork: Review and Update

Vascular dysfunction precedes hypertension associated with a blood pressure locus on rat chromosome 12

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