Lens proteins

The findings discussed above suggest that the presence of Met(O) residues in a-l-PI and lens proteins might account for some of the observed clinical manifestations. It is of interest to speculate that Met(0)-peptide reductase may function as a repair enzyme to prevent the accumulation of Met(O) residues in most proteins. Whether in those examples as discussed above, the accumulation of Met(O) in proteins is a result of an overwhelming increase in the synthesis of biological oxidants and/or a decrease in the ability to either destroy the biological oxidants or reduce the Met(O) residues in the proteins is not known. If it is the latter, this could be due to a decrease in the reductase itself or to some impairment in the reducing system that the enzyme requires. 

In addition to a-l-PI, there are other examples of the presence of Met(O) residues in proteins isolated from biological material. Proteins found in lens tissue are particularly susceptible to photooxidation and because of the long half-lives of these proteins, any oxidation could be especially detrimental. In this tissue, protein synthesis is localized to the outer region of the tissue and most proteins are stable for the life of the tissue - ". It is thus somewhat surprising that not only is there no Met(O) residues in the young normal human lens but even in the old normal human lens only a small amount of Met(O) residues is found . However, in the cataractous lens as much as 65% of the Met residues of the lens proteins are found in the form of Met(0) . Whether this increase in Met(O) content in these proteins is a cause or a result of the cataracts is not known. In order to determine whether the high content of Met(O) in the cataractous lens is related to a decreased activity of Met(0)-peptide reductase, the level of this enzyme was determined in normal and cataractous lenses. It can be seen from Table 9 that there are no significant differences between the levels of Met(0)-peptide reductase in normal and cataractous lenses. In spite of these results, however, it is still possible that the Met(0)-peptide... 

Chromatographic evidence supporting the similarity of the yellow chromophores isolated from aged human brunescent cataract lenses and calf lens proteins modified... 

FIGURE 10.13 The TLC profiles of labeled peaks isolated from [U- C]ascorbic-acid-modified calf lens protein obtained from Bio-Gel P-2 chromatography. Peaks 2 to 7 were spotted on a preparative silica gel TLC plate and developed with ethanol/ammonia (7 3, v/v). The fluorescence in each lane was detected by irradiation with a Wood s lamp at 360 nm, and the pattern of radioactivity was determined by scanning the plate with AMBIS imaging system. (Reprinted with permission from Cheng, R. et al., Biochim. Biophys. Acta, 1537, 14-26, 2001. Copyright (2001) Elsevier.)... 

Small angle X-ray-scattering studies and light-scattering studies of lens extracts show that the transparency of the lens is the result of the short-range spatial order of lens proteins (Delaye and Tardieu, 1983). The molecular structure of the individual crystallins is well ordered even though the overall pattern in the lens may appear chaotic. 

A number of diflFerent animal models of uveitis have been developed) including that induced by organ-specific ocular antigens such as retinal S-antigen, rhodopsin and lens protein (Wacker et al., 1977 Rao et al., 1979). Other models are based on the injection of proteins foreign to the host, such as intravitreal injections of albumin or 7-globulin (Zimmerman and Silverstein, 1959 Kaplan etal., 1979). More recently, a third group of models has been developed based on the injection of inflammatory mediators such as interleukins-1 and 2, and tumour necrosis factor (Bhattacherjee and Henderson, 1987 ... 

Dillon, J. (1984). Photolytic changes in lens proteins. Curr. Eye Res. 3, 145-150. 

Fig. 3 Transition energy for S0 — Sj (red) and S0 — CT(black) for a tryptophan during a 2 ns QM-MM trajectory of the human eye lens protein yD-crystallin showing typical fluctuations due to rapid changes in local electrostatic potentials at the atoms of the chromophore. This Trp has a low quantum yield because the CT state is near the Sj state much of the time. Heterogeneity in lifetime and wavelength are evident in both states because regions of 100 ps are seen having distinctly different average energies...

Slight SH, Prabhakaram M, Shin DB, Feather MS and Ortwerth BJ (1992) The extent of N-(carboxymethyl)lysine formation in lens proteins and polylysine by the autoxidation products of ascorbic acid. Biochim Biophys Acta 1117, 199-206. 

Biological samples such as bacteria and viruses have been studied by SdFFF as well as FIFFF. These two techniques provided bacterial number, density, size, and mass distributions of bacterial cells of diverse shapes and sizes, molecular weights, sizes, densities, and diffusivities of viruses. SdFFF has been used to analyze protein particles, including casein derived from nonfat dry milk, albumin microspheres, and particles in cataractous lenses originating from the aggregation of lens proteins. 

Exposure of self-reactive T lymphocytes to antigens previously sequestered from the immune system (eg, lens protein, myelin basic protein). 

What is most remarkable is that cells can produce proteins with strikingly different properties and activities by joining the same 20 amino acids in many different combinations and sequences. From these building blocks different organisms can make such widely diverse products as enzymes, hormones, antibodies, transporters, muscle fibers, the lens protein of the eye, feathers, spider webs, rhinoceros horn, milk proteins, antibiotics, mushroom poisons, and myriad other substances having distinct biological activities (Fig. 3-1). Among these protein products, the enzymes are the most varied and specialized. Virtually all cellular reactions are catalyzed by enzymes. 

A common problem with lenses is cataract, a term that describes any loss of opacity or excessive coloration. There are many kinds of cataract, most of which develop in older persons.560 562 Since lens proteins are so long-lived deamidation of some asparagine occurs. However, the reactions are slow. One of the asparagines in a crystalline has a half-life of 15-20 years, and some glutamines are undamaged after 60 years.575... 

The role of the IF, and particularly the keratin filament system, in resisting the forces of mechanical stress has been well established. However, IFs also play a role in countering metabolic stress. Perhaps the best example is the cytoprotective role played by the simple epithelial keratins, K8/18. However, vimentin, desmin, peripherin, GFAP, the lens proteins phakinin, and filensin and other keratins have also been shown to associate with members of the small heat shock protein (HSP) family, including HSP27 and aB-crystallin (reviewed in Coulombe and Wong, 2004 Marceau et al., 2001 Nicholl and Quinlan, 1994). 

The frequency of the amide I peak observed in the lens is sensitive to protein secondary structure. From its absolute position at 1672 cm-1, which is indicative for an antiparallel pleated 3-sheet structure, and the absence of lines in the 1630-1654 cm-1 region, which would be indicative of parallel (1-sheet and a-helix structures, the authors could conclude that the lens proteins are all organized in an antiparallel, pleated 3-sheet structure [3]. Schachar and Solin [4] reached the same conclusion for the protein structure by measuring the amide I band depolarization ratios of lens crystallins in excised bovine lenses. Later, the Raman-deduced protein structure findings of these two groups were confirmed by x-ray crystallography. 

Incubation of D-xylose with an aqueous solution of bovine lens protein gave both xylitol and xylonic acid. Studies of the reaction under a variety of conditions suggest that both the reduction and oxidation reactions are protein (possibly enzyme) catalyzed and appear to be unique to lens... 

Marker Lens protein Skin collagen Reference... 

P. S. Padayatti, A. S. Ng, K. Uchida, M. A. Glomb, and R. H. Nagaraj, Argpyrimidine, a blue fluorophore in human lens proteins High levels in brunescent cataractous lenses, Invest. Ophthal. Visual Sci., 2001, 42, 1299-1304. 

M. U. Ahmed, E. B. Frye, T. P. Degenhardt, S. R. Thorpe, and J. W. Baynes, Nc-(Carboxyethyl)lysine, a product of the chemical modification of proteins by methylgly-oxal, increases with age in human lens proteins, Biochem. J., 1997, 324, 565-570. 

M. C. Wells-Knecht, T. G. Huggins, D. G. Dyer, S. R. Thorpe, and J. W. Baynes, Oxidized amino acids in lens protein with age. Measurement of o-tyrosine and dityrosine in the aging human lens, J. Biol. Chem., 1993, 268, 12348-12352. 

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