Additionally we were prompted to validate the protective eff

Additionally, we were prompted to validate the protective effect of ALDH3A1 by utilizing a human corneal model. Cornea is located in the anterior segment of the eye and thus, is constantly exposed to various environmental stressors that affect the cellular oxidative balance and consequently lead to cellular oxidative stress (Cejka and Cejkova, 2015). Considering that oxidative stress significantly affects protein folding and induces the aggregation of proteins, through their oxidation (Nita and Grzybowski, 2016), we investigated the effect of ALDH3A1 over-expression on the viability of the human corneal epithelial HCE-2 5-fluorocytosine under oxidative stress conditions. Our results demonstrated that the expression of ALDH3A1 significantly inhibited the cytotoxic effects of both tert-butyl hydroperoxide and H2O2 on HCE-2 cells. In summary, the present study showed that ALDH3A1 displays significant chaperone-like activity in vitro, which was was further confirmed in bacterial and mammalian experimental models under the influence of thermal and/or oxidative stress. Nevertheless, future studies need to validate and fully characterize the chaperone-like potential of ALDH3A1 in mammalian corneal epithelial cells under variable stress conditions. Furthermore, the study of ALDH3A1 surface hydrophobic anisotropies will allow us to determine whether the mechanisms by which the chaperone activity of ALDH3A1 is accomplished share any similarities with those of α-crystallin. Future research will undoubtedly reveal new insights into the currently unknown mechanisms of the chaperone function of ALDH3A1.
Acknowledgments Funding: This research has been co-financed by the European Union (European Social Fund-ESF) and Greek national funds through the Operational Program “Education and Lifelong Learning” of the National Strategic Reference Framework (NSRF) − Research Funding Program: Heracleitus II. Investing in knowledge society through the European Social Fund.
Introduction Betaine Aldehyde Dehydrogenase (betaine aldehyde: NAD(P)+ oxidoreductase, (E.C. 1.2.1.8; BADH) belongs to the superfamily of aldehyde dehydrogenases (ALDH9), implicated in the aldehyde detoxification [1]. BADH catalyze the irreversible oxidation of betaine aldehyde (BA) to glycine betaine (GB) and is essential for polyamine catabolism, γ-aminobutyric acid synthesis, and carnitine biosynthesis. The BADH from the liver of the Sprague-Dawley rats was purified to homogeneity from the cytosolic [2] and mitochondrial [3] fraction, demonstrating that significant enzyme activity is located in the cytosol. Both enzymes recognize the betaine aldehyde, γ-aminobutyraldehyde and γ-trimethylaminobutyraldehyde as a substrate, with lower Km values for the γ-aminobutyraldehyde substrate. The BADH from rat intestinal mucosa was purified and characterized [4], demonstrating that this enzyme shares some properties with the E3 isoenzyme [5]. This support that ALDH9 enzymes in mammals become from the same gene. The BADH activity distribution in mammals among different tissues reveals that heart muscle presented lower enzyme activity in contrast with other organs as skeletal muscle and liver [6]. The lower levels of BADH in healthy heart could explain the lack of BADH investigation in this tissue. Nevertheless, it should be considered that BADH is described as a stress response enzyme and that higher levels could be found under stress conditions. The physiological cardiac hypertrophy induced by pregnancy is a reversible process characterized by an increase in chamber dimension and wall thickness, followed by an increase in the myocyte length and width [7]. The physiological cardiac hypertrophy is caused by a constant volume overload in the heart, that reduce the contractive capacity required for the blood pumping, affects the shape, size and relaxing properties of the heart [8]. The hypertrophy exposes the cardiac myocytes to hypoosmotic challenge, considering that cardiac cells have less capacity for water permeability compared with renal or blood cells, this compromise the response mechanism for short and long term osmotic challenge [9]. The osmotically-induced genes and proteins in cardiomyocytes focused on their survival are described, identifying hundreds of genes and proteins associated with distinct pathways in cardiovascular diseases [10], [11], [12]. However, further studies are needed to confirm the specific role of the proteins analyzed in massive screening.