Lens Proteins and Aging

Hoenders, Herman J.; Bloemendal, H.

doi:10.1093/geronj/38.3.278

Cited by 79 publications

(45 citation statements)

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“…In order to convert CPM/mg to nanomoles Glc-Lys per nanomole lens protein, the following assumptions were made: the average molecular weight of the lens crystallin polypeptides is 20,000 (19)(20)(21); the ketone functions of glucosyl-valine in Hb Al, and glucosyl-lysine in crystallin label with 3H-BH4 with equal efficiency. The reducing capacity of the unlabeled borohydride was 98±2% as measured colorimetrically by the (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The protein samples were incubated for 24 h, 4VC, with a 100-fold molar excess of Na-3H-borohydride (New England Nuclear, Boston, MA), originally 340 mCi/mmol, which had been diluted with nonradioactive NaBH4 (Sigma Chemical Co.) to a specific radioactivity of 100 mCi/mmol. A polypeptide chain molecular weight of 20,000 was assumed for the lens crystallin monomers (19)(20)(21). A sample containing 1.0 mg of human Hb fraction Al, was also reacted with 3H-borohydride under the same conditions (molecular weight of Hb A,, dimer equals 31,000).…”

Section: Methodsmentioning

confidence: 99%

“…The cells at the center, or nucleus, of the lens are thought to be as old as the organism itself. The proteins in the fiber cells do not turn over (or do so exceedingly slowly), so that some protein at the center of the lens is there for the lifetime of the individual (19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

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Nonenzymatic glycation of human lens crystallin. Effect of aging and diabetes mellitus.

Garlick¹,

Mazer²,

Chylack³

et al. 1984

J. Clin. Invest.

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Abstract. We have examined the nonenzymatic glycation' of human lens crystallin, an extremely long-lived protein, from 16 normal human ocular lenses 0.2-99 yr of age, and from 11 diabetic lenses 52-82-yrold. The glucitol-lysine (Glc-Lys)2 content of soluble and insoluble crystallin was determined after reduction with 3H-borohydride followed by acid hydrolysis, boronic acid affinity chromatography, and high pressure cation exchange chromatography. Normal lens crystallin, soluble and insoluble, had 0.028±0.011 nanomoles GlcLys per nanomole crystallin monomer. Soluble and insoluble crystallins had equivalent levels of glycation. The content of Glc-Lys in normal lens crystallin increased with age in a linear fashion. Thus, the nonenzymatic glycation of nondiabetic lens crystallin may be regarded as a biological clock. The diabetic lens crystallin samples (n = 11) had a higher content of Glc-Lys Receivedfor publication 9 April 1984.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Nonenzymatic glycation of human lens crystallin. Effect of aging and diabetes mellitus.

Garlick¹,

Mazer²,

Chylack³

et al. 1984

J. Clin. Invest.

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“…This process is among the most commonly occurring posttranslational modifications, although its role is not completely understood. Some investigators have considered deamidation to be an undesirable form of protein damage, and it has been implicated in several pathologic conditions, including cataracts (27,28) and Alzheimer's disease (29). Another possibility is that deamidation is simply a dysregulation of normally occurring processes in a cell (30,31).…”

Section: Potential Early Biomarkers For Ropmentioning

confidence: 99%

A Potential Biomarker in the Cord Blood of Preterm Infants Who Develop Retinopathy of Prematurity

et al. 2007

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ABSTRACT:Preterm infants are at risk of developing sepsis, necrotizing enterocolitis (NEC), chronic lung disease (CLD), and retinopathy of prematurity (ROP). We used high-throughput mass spectrometry to investigate whether cord blood proteins can be used to predict development of these morbidities. Cord blood plasma from 44 infants with a birth weight of Ͻ1500 g was analyzed by surfaceenhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF). Six infants developed ROP Նstage II, 10 CLD, three sepsis, and one NEC. We detected 814 protein signals representing 330 distinct protein species. Nineteen biomarkers were associated with development of Նstage II ROP [false-discovery rate (FDR) Ͻ5%] and none with CLD. Several proteins with molecular weight (M r ) 15-16 kD and pI 4 -5 were detected with increased abundance in infants with ROP, while similar M r proteins with pI 7-9 were less abundant in these patients. Sodium dodecylsulfatepolyacrylamide gel electrophoresis (SDS-PAGE) and sequence analysis identified these proteins as ␣-, ␤-, and ␥-globin chains. Partial deamidation of Asn139 in ␤-globin chains was observed only in the pI 4 -5 proteins. We conclude that there are several promising biomarkers for the risk of ROP. Deamidation of globin chains is especially promising and may indicate underlying prenatal pathologic mechanisms in ROP. Validation studies will be undertaken to determine their clinical utility. (Pediatr Res 61: 215-221, 2007) P reterm infants are at risk of developing complications such as sepsis, NEC, CLD, and ROP (1-6). Approximately 0.3%-3.2% of low birth weight infants (501-1500 g) have more than one of these morbidities (3). The reason why some preterm infants of the same gestational age have a mild neonatal course while others go on to develop particular morbidities is of great interest to neonatologists. It has been hypothesized that the release of proinflammatory cytokines such as interleukin (IL)-6, IL-1␤, IL-8, tumor necrosis factor ␣ in amniotic fluid and other body fluids before birth may play a role in several adverse outcomes, including CLD, periventricular leukomalacia (PVL), and cerebral palsy (4,7-9).Biomarker molecules that could identify the onset of or susceptibility for a particular disease would be valuable. Low molecular weight proteins present in plasma offer the potential to be such biomarkers. Several techniques can be used to identify these proteins or potential biomarkers. Antibody arrays can be useful in detection of proteins in disease states where there is a known panel of proteins implicated in the disease process. However, other methods for detection are needed in multifactorial diseases where the identity of the protein involved in the molecular pathogenesis is not yet known. Two-dimensional (2-D) electrophoresis is one such method that is useful as a screening technique for identification of proteins Ͼ20 kD. Another strategy is to screen and identify protein biomarkers using mass spectrometry (MS), an analytical technique that identifies unk...

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“…Aging of the human eye lens is accompanied by a decrease in nuclear protein content [1] and changes in crystallin composition and macromolecular conformation of proteins [2][3][4][5][6][7]. Conformational protein changes, including dehydration/hydration, formation of aggregates, changes in backbone and side-chains are early signs of increased light scatter, possibly preluding cataract formation.…”

Section: Introductionmentioning

confidence: 99%

Local variations in protein structure in the human eye lens: a Raman microspectroscopic study

Smeets

Vrensen

Otto

et al. 1993

Biochimica et Biophysica Acta (BBA) - Protein Structure and Mol

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Confocal Raman microspectroscopy was used to monitor local and age-related changes in protein conformation in human eye lenses. In clear human lenses of varying age (range 17-80 years) spectra were recorded along the visual axis, using laser light of 660 nm wavelength. The Raman vibrations in the 650-1750 cm -1 spectral region were analyzed. Difference spectra between central core and different positions along the visual axis were calculated after calibration for protein content using the I(1450) cm-1 CH2/CH 3 vibration peak. Tryptophan content was quantified using the peak at 760 cm-~ calibrated for protein. Changes in the 'exposed' vs. 'buried' position of tryptophan were analyzed using the peak heights at I(880) and 1(760) cm-L The difference spectra revealed an excess of tryptophan, tyrosine, phenylalanine,/3-sheet conformation and molecules or molecular groups responsible for a 1425 cm-1 peak in the core region in all lenses investigated. The excess peaks disappeared at about 0.6-0.9 mm below the surface. The tryptophan content increased from superficial to deep layers, levelling off between 0.4-0.8 mm below the surface. Upon aging, the tryptophan content increases in the core not in the cortex. No changes in the 'exposed' vs. 'buried' position of tryptophan were observed. Changes in tryptophan and tyrosine probably reflect the maturational shift from cortex to core in the relative content of a, /3 and ~/ crystallines. The age-related increase in tryptophan in the core may reflect the preferential breakdown by endo-and exopeptidases of a-crystallins damaged upon aging. The increase in /3-sheet conformation may indicate a post-translational shift in secondary conformation upon aging. These changes in protein conformation are largely completed in a small superficial zone, i.e., in the early life span of the crystallins.

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Lens Proteins and Aging

Cited by 79 publications

References 0 publications

Nonenzymatic glycation of human lens crystallin. Effect of aging and diabetes mellitus.

Nonenzymatic glycation of human lens crystallin. Effect of aging and diabetes mellitus.

A Potential Biomarker in the Cord Blood of Preterm Infants Who Develop Retinopathy of Prematurity

Local variations in protein structure in the human eye lens: a Raman microspectroscopic study

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