Effect of dicarbonyl-induced browning on alpha-crystallin chaperone-like activity: physiological significance and caveats of in vitro aggregation assays

Kumar, Mukesh; Reddy, P. Yadagiri; Kumar, P. Anil; Surolia, Ira; Reddy, G. Bhanuprakash

doi:10.1042/bj20031633

Cited by 106 publications

(93 citation statements)

References 48 publications

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“…Consistent with this is the independent observation that the heat shock protein HSP27 interacts with the insulin-like growth factor receptor 1 and its signal transducer, the serine/threonine kinase protein Akt, which together modulate adipocyte metabolism (52,53). Diabetes alters the metabolism of the chaperone crystallin ␣, increasing its glycation status (43,44). In the lens of the eye, this biochemical change contributes to cataract formation; its effect in adipose tissue, if any, remains to be determined.…”

Section: Resultssupporting

confidence: 54%

“…The heat shock proteins serve as chaperones, controlling protein folding in the endoplasmic reticulum and their subsequent intracellular trafficking (42). There is a growing body of literature linking chaperone-like molecules to adipogenesis, obesity, and diabetes (43)(44)(45)(46). For example, adipogenesis in 3T3-L1 cells is accompanied by increased expression of the chaperone-related immunophilin, FK-binding protein 51 (47).…”

Section: Resultsmentioning

confidence: 99%

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Proteomic Analysis of Primary Cultures of Human Adipose-derived Stem Cells

DeLany

Floyd

Zvonic

et al. 2005

Molecular & Cellular Proteomics

132

128

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Adipogenesis plays a critical role in energy metabolism and is a contributing factor to the obesity epidemic. This study examined the proteome of primary cultures of human adipose-derived adult stem (ADAS) cells as an in vitro model of adipogenesis. Protein lysates obtained from four individual donors were compared before and after adipocyte differentiation by two-dimensional gel electrophoresis and tandem mass spectroscopy. Over 170 individual protein features in the undifferentiated adipose-derived adult stem cells were identified. Following adipogenesis, over 40 proteins were up-regulated by >2-fold, whereas 13 showed a >3-fold reduction. The majority of the modulated proteins belonged to the following functional categories: cytoskeleton, metabolic, redox, protein degradation, and heat shock protein/chaperones. Additional immunoblot analysis documented the induction of four individual heat shock proteins and confirmed the presence of the heat shock protein 27 phosphoserine 82 isoform, as predicted by the proteomic analysis, as well as the crystallin ␣ phosphorylated isoforms. These findings suggest that the heat shock protein family proteome warrants further investigation with respect to the etiology of obesity and type 2 diabetes. Molecular & Cellular Proteomics 4:731-740, 2005.Obesity is a health problem of epidemic proportions. It is estimated that in 2000 over 60% of adults are overweight (BMI 1 Ͼ 25) and that 30% are obese (BMI Ͼ 30); this compares to levels of 46 and 14%, respectively, in 1980. Obesity and increased adiposity are associated clinically with the onset of insulin resistance, dysfunctional glucose sensing and utilization, hypertension, and hypertriglyceridemia, all contributing to the pathologic sequelae of type 2 diabetes. Paradoxically type 2 diabetes also occurs in patients with inherited or acquired forms of lipodystrophy or loss of adipose tissue depots (1, 2). Lipodystrophy occurs through defects in genes associated with triglyceride metabolism or as a consequence of antiretroviral therapy in human immunodeficiency viruspositive patients (1, 2). Animal models confirm these clinical observations; multiple strains of transgenic mice with a lipodystrophic phenotype exhibit type 2 diabetes (3-5). Diabetes in these animals responds not to insulin therapy but to transplantation of subcutaneous adipose tissue or to leptin treatment (3-5). These clinical and experimental observations have led to the hypothesis that a failure in adipocyte differentiation is a critical etiologic factor leading to type 2 diabetes (6 -8). Danforth (6) and others postulate that in obese individuals adipose tissue depots have already committed all of their stem cell reserves to the adipocyte lineage and have lost their capacity to create new adipocytic cells (6 -8). In the face of excess energy balance, both obese and lipodystrophic individuals deposit triglycerides in ectopic sites, such as muscle and liver, thereby contributing to the metabolic dysfunction associated with type 2 diabetes (increased hepatic glucon...

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Section: Resultssupporting

confidence: 54%

Section: Resultsmentioning

confidence: 99%

Proteomic Analysis of Primary Cultures of Human Adipose-derived Stem Cells

DeLany

Floyd

Zvonic

et al. 2005

Molecular & Cellular Proteomics

132

128

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“…Elevated activity of aldose reductase and increased production of sorbitol have been implicated for cataractogenesis in diabetic humans and experimental diabetic animals (89). Studies from our laboratory and by others have reported that in vitro nonenzymatic glycation of a-crystallin resulted in the decreased chaperone activity, which is associated with crosslinking and formation of HMM aggregates (55,56,90,91). Moreover, glycation-induced structural changes in acrystallin are comparable with changes manifested in a-crystallin during diabetic cataract (87).…”

Section: Molecular Chaperone-like Function Of A-crystallin and Eye Lesupporting

confidence: 55%

Modulation of α‐crystallin chaperone activity: A target to prevent or delay cataract?

Pasupulati

Reddy

2009

IUBMB Life

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SummaryCataract, loss of eye lens transparency, is the leading cause of blindness worldwide. a-Crystallin, initially known as one of the major structural proteins of the eye lens, is composed of two homologous subunits aA-and aB-crystallins. It is convincingly established now that a-crystallin functions like a chaperone and plays a decisive role in the maintenance of eye lens transparency. The functional ability of a-crystallin subunits is to act in cooperation as molecular chaperones to prevent the cellular aggregation and/or inactivation of client proteins under variety of stress conditions. However, chaperone-like activity of a-crystallin could be deteriorated or lost during aging or under certain clinical conditions because of various genetic and environmental factors. This review will focus specifically on relevance of a-crystallin chaperone function to lens transparency. In particular, we reviewed the studies that demonstrate the modulation of a-crystallin chaperone-like activity and discussed the possibility of chaperone-like activity of a-crystallin as a potential target to prevent or delay the cataractogenesis.2009 IUBMB IUBMB Life, 61(5): [485][486][487][488][489][490][491][492][493][494][495] 2009

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“…In another study, calf lens ␣A-crystallin was found to be more hydrophobic but showed lower chaperone activity than ␣B-crystallin at room temperature (18). In vitro modification of bovine ␣-crystallin with methylglyoxal enhanced the chaperone-like activity, particularly in aggregation assays, although hydrophobicity showed a decrease (27). Moreover, apparent differences in the temperaturedependent behavior of ␣A-and ␣B-crystallins with respect to chaperone activity, hydrophobicity, and oligomeric size necessitate a critical evaluation of the role of hydrophobicity in ␣A-crystallin and ␣B-crystallin function.…”

Section: Resultsmentioning

confidence: 99%

Insights into Hydrophobicity and the Chaperone-like Function of αA- and αB-crystallins

Kumar

Kapoor

Sinha

et al. 2005

Journal of Biological Chemistry

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␣-Crystallin, composed of two subunits, ␣A and ␣B, has been shown to function as a molecular chaperone that prevents aggregation of other proteins under stress conditions. The exposed hydrophobic surfaces of ␣-crystallins have been implicated in this process, but their exact role has not been elucidated. In this study, we quantify the hydrophobic surfaces of ␣A-and ␣B-crystallins by isothermal titration calorimetry using 8-anilino-1-napthalenesulfonic acid (ANS) as a hydrophobic probe and analyze its correlation to the chaperone potential of ␣A-and ␣B-crystallins under various conditions. Two ANS binding sites, one with low and another with high affinity, were clearly detected, with ␣B showing a higher number of sites than ␣A at 30°C. In agreement with the higher number of hydrophobic sites, ␣B-crystallin demonstrated higher chaperone activity than ␣A at this temperature. Thermodynamic analysis of ANS binding to ␣A-and ␣B-crystallins indicates that high affinity binding is driven by both enthalpy and entropy changes, with entropy dominating the low affinity binding. Interestingly, although the number of ANS binding sites was similar for ␣A and ␣B at 15°C, ␣A was more potent than ␣B in preventing aggregation of the insulin B-chain. Although there was no change in the number of high affinity binding sites of ␣A and ␣B for ANS upon preheating, there was an increase in the number of low affinity sites of ␣A and ␣B. Preheated ␣A, in contrast to ␣B, exhibited remarkably enhanced chaperone activity. Our results indicate that although hydrophobicity appears to be a factor in determining the chaperone-like activity of ␣-crystallins, it does not quantitatively correlate with the chaperone function of ␣-crystallins.

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Effect of dicarbonyl-induced browning on alpha-crystallin chaperone-like activity: physiological significance and caveats of in vitro aggregation assays

Cited by 106 publications

References 48 publications

Proteomic Analysis of Primary Cultures of Human Adipose-derived Stem Cells

Proteomic Analysis of Primary Cultures of Human Adipose-derived Stem Cells

Modulation of α‐crystallin chaperone activity: A target to prevent or delay cataract?

Insights into Hydrophobicity and the Chaperone-like Function of αA- and αB-crystallins

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