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KMID : 1011420230280030255
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Journal of Korean Ophthalmic Optics Society
2023 Volume.28 No. 3 p.255 ~ p.262
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Induction of 5-lipoxygenase by 4-hydroxynonenal via Nitric Oxide Generation in Vascular Smooth Muscle Cells
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Lee Ji-Young
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Abstract
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Purpose : The induction of 5-lipoxygenase (5-LO) by 4-hydroxynonenal (HNE) is of significant interest for understanding the mechanisms underlying the homeostasis of the cellular redox balance, leading to retinal dysfunction. However, the roles of these mediators in vascular smooth muscle cells (VSMC) remain unclear. This study investigated whether the induction of 5-LO by HNE was mediated by nitric oxide (NO) generation in VSMC.
Methods : A10 cells were preincubated in DMEM containing HNE after preincubation with NO inhibitors. The gene expression levels of 5-LO were analyzed by western blotting and reverse transcriptase-polymerase chain reaction. Intracellular NO formation was measured by fluorescence using 4,5-diaminofluorescein as a specific NO indicator using flow cytometry.
Results : The fluorescence profiles increased in a time-dependent manner in cells treated with 1mM HNE. These data indicate that HNE induced NO generation in VSMC. NO inhibitors prevent HNE-induced NO generation and 5-LO expression. In addition, the results showed the upregulation of 5-LO mRNA levels by HNE. This suggests that HNE plays a role in regulating 5-LO at the transcriptional level without the possibility of post-translational modification.
Conclusions : These findings suggest that HNE-induced oxidative stress, including NO generation, is an important risk factor for retinopathy development via 5-LO gene expression in VSMC. The induction of 5-LO by HNE in VSMC is mediated by NO generation, leading to the deterioration of vasculature homeostasis and subsequent retinal dysfunction, such as retinopathy.
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KEYWORD
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5-Lipoxygenase, 4-Hydroxynonenal, NO, Retinopathy, VSMC
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