4-Hydroxyhexenal- and 4-Hydroxynonenal-Modified Proteins in Pterygia

Abstract

Oxidative stress has been suspected of contributing to the pathogenesis of pterygia. We evaluated the immunohistochemical localization of the markers of oxidative stress, that is, the proteins modified by 4-hydroxyhexenal (4-HHE) and 4-hydroxynonenal (4-HNE), which are reactive aldehydes derived from nonenzymatic oxidation of n-3 and n-6 polyunsaturated fatty acids, respectively. In the pterygial head, labeling of 4-HHE- and 4-HNE-modified proteins was prominent in the nuclei and cytosol of the epithelium. In the pterygial body, strong labeling was observed in the nuclei and cytosol of the epithelium and proliferating subepithelial connective tissue. In normal conjunctival specimens, only trace immunoreactivity of both proteins was observed in the epithelial and stromal layers. Exposures of ultraviolet (330 nm, 48.32 ± 0.55 J/cm2) or blue light (400 nm, 293.0 ± 2.0 J/cm2) to rat eyes enhanced labeling of 4-HHE- and 4-HNE-modified proteins in the nuclei of conjunctival epithelium. Protein modifications by biologically active aldehydes are a molecular event involved in the development of pterygia.

Molecular Basis of Pterygium Development

“…The ROS formed as a consequence of UV-B radiation have the potential to cause lipid peroxidation in cellular membranes, thus promoting the degeneration of polyunsaturated fatty acids (PUFAs) into various compounds, including the reactive aldehydes 4-hydroxyhexenal (4-HHE) and 4-hydroxynonenal (4-HNE). 51,52 These molecules have been found in increased levels throughout the pterygial specimens, including the head, where the corneal-migration occurs at the front of the pterygium, and the body, where active proliferation of subepithelial connective tissues occurs. 52 4-HHE and 4-HNE have the potential to modify proteins and affect their normal function by reacting with histidine, cysteine, and lysine residues.…”

“…51,52 These molecules have been found in increased levels throughout the pterygial specimens, including the head, where the corneal-migration occurs at the front of the pterygium, and the body, where active proliferation of subepithelial connective tissues occurs. 52 4-HHE and 4-HNE have the potential to modify proteins and affect their normal function by reacting with histidine, cysteine, and lysine residues. 53 Such protein modifications have been found to be prominent in pterygium tissue, as opposed to normal conjunctiva.…”

“…53 Such protein modifications have been found to be prominent in pterygium tissue, as opposed to normal conjunctiva. 52 Also, a significant increase in malone dialdehyde (MDA), another marker of lipid peroxidation caused by UV-B radiation, has been observed in pterygium tissues with consistent decrease in the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx), leading to ROS accumulation that causes DNA damage. 44 Nevertheless, the enzyme peroxiredoxin 2, another antioxidant enzyme which lowers peroxide and hydroperoxide, has been found overexpressed in pterygium epithelium by western blotting and through a proteomic approach carried out in 12 samples.…”

The Oxidant Role of 4-Hydroxynonenal in Corneal Epithelium

“…4-Hydroxynonenal has been previously reported to be associated with ocular surface diseases 9 10 11 12 . The novel evidence of this present study demonstrated that 4-HNE contributes to oxidative stress in corneal epithelium.…”

“…Extensive research suggests that oxidative stress plays vital roles in the pathogenesis of many ocular diseases. Multiple clinical and experimental studies demonstrated that 4-Hydroxynonenal is associated with some ocular surface diseases, including granular corneal dystrophy, atopic keratoconjunctivitis, pterygium, and dry eye 9 10 11 12 , as well as cataract 13 , age related macular degeneration (AMD) 14 and diabetic retinopathy 15 , while the role and the underlying mechanism of 4-HNE in the eyes remain largely unknown. The aim of this present study was to focus on and investigate the association between 4-HNE and oxidative stress in the corneal epithelium and explore the underlying mechanistic.…”