International Journal of Radiation Research

en Hint1 mitigates high glucose- and radiation-induced apoptosis and inflammation in human retinal pigment epithelial cells through inhibiting the NF-κB pathway Radiation Biology Radiation Biology تحقيق بديع Original Research <div style="text-align: justify;">Background: Histidine triad nucleotide-binding protein 1 (Hint1) has been associated with inflammation, apoptosis, and the DNA damage response. However, its potential role in RPE injury induced by high glucose and/or radiation is unclear. We evaluated the protective effects of Hint1 against high-glucose and irradiation-induced RPE cell injury and the underlying mechanism involved the NF-κB pathway. Materials and Methods: The expression of Hint1 was determined in retinas from mice with type 1 diabetes and in human RPE cells with high-glucose and/or irradiation injury. Modulation of Hint1 protein levels was achieved through Hint1-overexpression and knockdown. Cellular apoptosis, DNA damage, cytokine production, and NF-κB activity were measured by flow cytometry, γH2AX immunofluorescence/Western blot, real-time PCR, ELISA, Western blot, and p65 translocation assay. BAY 11-7082 was used for mechanism validation. Result: Expression of Hint1 was down-regulated in diabetic retinal tissues and in ARPE-19 cells under combined exposure to hyperglycemia and radiation conditions with the most severe downregulation seen in the case of combined stimuli. The combination increased apoptosis, γ-H2AX levels, TNF-α, IL-6, and IL-8 expression, and nuclear translocation of phosphorylated p65. Overexpression of Hint1 reduced apoptosis, DNA damage, and cytokine release, whereas knockdown of Hint1 increased them. Inhibition of NF-κB partially reversed the detrimental effects of Hint1 deficiency. Conclusion: Hint1 attenuates high-glucose- and radiation-induced RPE cell injury, particularly under combined stress, at least in part by suppressing NF-κB activation. These findings suggest that the Hint1/NF-κB axis may represent a potential therapeutic target for retinal injury associated with diabetes and radiotherapy.</div> Histidine triad nucleotide-binding protein 1, diabetic retinopathy, retinal pigment epithelium, radiation injuries, apoptosis 819 829 http://ijrr.com/browse.php?a_code=A-10-1-1582&slc_lang=en&sid=1 W. Luo 7900319475328460034439 7900319475328460034439 No Department of Ophthalmology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu Province, China R. Xu 7900319475328460034440 7900319475328460034440 No School of Public Health, Tianjin Medical University, Tianjin, China P. Wu wupch@lzu.edu.cn 7900319475328460034441 7900319475328460034441 Yes Department of Ophthalmology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu Province, China M. Yu 7900319475328460034442 7900319475328460034442 No Department of Ophthalmology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu Province, China W. Dong 7900319475328460034443 7900319475328460034443 No Department of Ophthalmology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu Province, China