Within ultraviolet radiation, ultraviolet B (UVB) is the most energetic and damaging to humans. At the protein level, UVB irradiation downregulates the expression of antioxidant enzymes leading to the accumulation of reactive oxygen species (ROS). Due to lacking of a global analysis of UVB-modulated corneal proteome, we investigate in vitro the mechanism of UVB-induced corneal damage to determine whether hyaluronic acid (HA) is able to reduce UVB irradiation-induced injury in human corneal epithelial cells. Accordingly, human corneal epithelial cell lines (HCE-2) were irradiated with UVB, followed by incubation with low molecular weight HA (LMW-HA, 100 kDa) or high molecular weight HA (HMW-HA, 1,000 kDa) to investigate the physiologic protection of HMW-HA in UVB-induced corneal injury, and to perform a global proteomic analysis. The data demonstrated that HA treatment protects corneal epithelial cells in the UVB-induced wound model, and that the molecular weight of HA is a crucial factor. Only HMW-HA significantly reduces the UVB-induced cytotoxic effects in corneal cells and increases cell migration and wound-healing ability. In addition, proteomic analysis showed that HMW-HA might modulate cytoskeleton regulation, signal transduction, biosynthesis, redox regulation, and protein folding to stimulate wound healing and to prevent these UVB-damaged cells from cell death. Further studies evidenced membrane-associated progesterone receptor component 1 (mPR) and malate dehydrogenase (MDH2) play essential roles in protecting corneal cells from UVB irradiation. This study reports on UVB-modulated cellular proteins that might play an important role in UVB-induced corneal cell injury and show HMW-HA to be a potential substance for protecting corneal cells from UVB-induced injury.
The metastatic status of oral cancer is highly associated with the overall survival rate of patients. Previous studies have revealed that the endogenous tryptophan metabolite 5-methoxytryptophan (5-MTP) can downregulate cyclooxygenase-2 expression; suppress tumor proliferation, migration, and invasion; and reduce the tumor size. To improve the understanding of the molecular mechanisms involved in the regulation of 5-MTP in the tumorigenesis of oral cancer, we conducted a comparative wound healing and transwell invasion assays. Our results revealed that 5-MTP reduce oral cancer cell migration and invasion ability. In addition, the results of an in vivo assay demonstrated that the growth of primary tumors was significantly inhibited by 5-MTP in OC3 oral cancer cells and in invasive OC3-I5 oral cancer cells. Moreover, enlarged spleens were observed in OC3-I5-implanted severe combined immunodeficiency mice although 5-MTP can inhibit spleen enlargement. Through comparative proteomics, we identified 32 differentially regulated protein spots by using 2D-DIGE/MALDI-TOF MS analyses. Some of the differentially regulated proteins such as amadillo-repeat-containing X-linked protein 1, phosphoglycerate kinase 1, tropomyosin alpha-1, and tropomyosin alpha-4 may be associated with the 5-MTP-dependent inhibition of oral cancer growth and metastasis. We conclude that 5-MTP plays a crucial role in inhibiting in vitro and in vivo cancer invasion and metastasis.
Diabetic retinopathy typically causes poor vision and blindness. A previous study revealed that a high blood glucose concentration induces glycoxidation and weakens the retinal capillaries. Nevertheless, the molecular mechanisms underlying the effects of high blood glucose induced diabetic retinopathy remain to be elucidated. In the present study, we cultured the retinal pigmented epithelial cell line ARPE-19 in mannitol-balanced 5.5, 25, and 100 mM glucose media and investigated protein level alterations. Proteomic analysis revealed significant changes in 137 protein features, of which 124 demonstrated changes in a glucose concentration dependent manner. Several proteins functionally associated with redox regulation, protein folding, or the cytoskeleton are affected by increased glucose concentrations. Additional analyses also revealed that cellular oxidative stress, including endoplasmic reticulum stress, was significantly increased after treatment with high glucose concentrations. However, the mitochondrial membrane potential and cell survival remained unchanged during treatment with high glucose concentrations. To summarize, in this study, we used a comprehensive retinal pigmented epithelial cell based proteomic approach for identifying changes in protein expression associated retinal markers induced by high glucose concentrations. Our results revealed that a high glucose condition can induce cellular oxidative stress and modulate the levels of proteins with functions in redox regulation, protein folding, and cytoskeleton regulation; however, cell viability and mitochondrial integrity are not significantly disturbed under these high glucose conditions.
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