Increased Susceptibility to Transglutaminase of Eye Lens Proteins Exposed to Activated Oxygen Species Produced in the Glucose-Glucose Oxidase Reaction

Abstract

In order to test whether a mild oxidative stress could promote the transglutaminase damaging effect on eye lens proteins, total lens soluble proteins and purified beta L-crystallin have been exposed to H2O2 slowly produced by the glucose-glucose oxidase reaction. Soon after the pretreatment, the substrate capacity of the lens proteins for an exogenous transglutaminase has been evaluated. Exposure to the oxidative stress increased the susceptibility of the lens proteins to transglutaminase. When ferrous ions were added to the preincubation medium, in order to convert the H2O2 into the hydroxyl radical, the increase was more evident.

Role of tissue transglutaminase-2 (TG2)-mediated aminylation in biological processes

“…Native ovalbumin, β-lactoglobulin, and bovine serum albumin are poor substrates for TG2 (Ikura et al 1984;Coussons et al 1992;de Jong et al 2001) and become excellent substrates after reduction of their disulfide bonds (Ikura et al 1984;Coussons et al 1992;de Jong et al 2001). In addition, exposure to oxidizing free radicals cause β-crystalline to function as a TG2 substrate (Brossa et al 1990;Seccia et al 1991). These data are consistent with the approach using computer program to analyze intrinsic disorder of several known TG2 substrates and they found intrinsic disorder of the structure also plays a role in serving as the substrates of TG2 (Csosz et al 2008).…”

Protein Oxidation in Human Stratum Corneum: Susceptibility of Keratins to Oxidation In Vitro and Presence of a Keratin Oxidation Gradient In Vivo

“…Possibly, transglutaminase, which catalyzes the formation of an amide bond between the γ-carbonyl group of glutamine and the ε-amino group of lysine and plays an important part in the formation of the cornified envelope (Greenberg et al, 1991), is involved in this dimerization. Notably, eye lens proteins were shown to be far more susceptible to transglutaminase catalyzed reactions when preincubated with reactive oxygen species (Brossa et al, 1990). Finally, an additional functional aspect that should be considered is that SC proteins, while being oxidized, may act as macromolecular anti-oxidants, preventing oxidative damage in subjacent epidermal layers.…”

Differential Gene Expression in Pseudoexfoliation Syndrome

“…TGase-2's effects may be further enhanced by the oxidative microenvironment in the anterior chamber of PEX eyes, 17 since oxidized proteins are known to be better substrates for TGase 2-mediated crosslinking. 32 Extracellular matrix metabolism and turnover is also greatly influenced by the large family of MMPs and their endogenous inhibitors TIMPs. 33 TIMP-1 controls the activity of most MMPs, in particular MMP-1, whereas TIMP-2 is the major inhibitor of MMP-2.…”