Lipopolysaccharide Enhances Genotoxicity by Activating GADD45G and NF- κ B in Human Corneal Epithelial Cells.
Ramachandran SamivelUmadevi SubramanianAdnan Ali KhanOmar KiratAli MasmaliTurki AlmubradSaeed AkhtarPublished in: Oxidative medicine and cellular longevity (2022)
As the prevalence of microbial keratitis increases, it creates an environment conducive to genotoxicity response. A potential connection between growth arrest and DNA-damage-inducible 45 gamma (GADD45G) gene expression has not been proven in the corneal epithelial cells. The aim of this study was to determine whether lipopolysaccharide (LPS) enhances genotoxicity, DNA damage, and inflammatory responses in human corneal epithelial cells (HCECs) in vitro . In a set of parameters, cytotoxicity, reactive oxygen species, mitochondrial membrane potential, DNA damage, inflammatory response, and apoptosis were assessed. LPS (1, 5, and 10 μ g/mL) treated HCECs were increased reactive oxygen species formation, mitochondrial membrane depolarization, and genotoxicity in a concentration-dependent manner. Similarly, NF- κ B, PARP1, and TP53 were also overexpressed in the LPS treated HCECs. 24 hours after LPS induction, micronucleus scoring, and proapoptotic factors were also increased. Among them, the GADD45G, NF- κ B, and γ H2AX were overexpressed both on the mRNA and protein levels in LPS (10 μ g/mL) treated HCECs. In our study, we show that the GADD45G signaling can trigger genotoxic instability in HCECs exposed to LPS. Therefore, understanding the factors contributing to infectious keratitis, such as GADD45G, NF- κ B, and γ H2AX signaling, may help to develop antigenotoxic and anti-inflammatory therapies for corneal dystrophy and epithelial cell remodeling.
Keyphrases
- inflammatory response
- lps induced
- dna damage
- oxidative stress
- anti inflammatory
- reactive oxygen species
- lipopolysaccharide induced
- signaling pathway
- toll like receptor
- gene expression
- dna repair
- endothelial cells
- optical coherence tomography
- nuclear factor
- wound healing
- pi k akt
- risk assessment
- endoplasmic reticulum stress
- induced pluripotent stem cells
- human health
- climate change
- cell proliferation