在耐火性突发感神经听力损失中,HIF-1α的上调调节
Wandong She1,2, Ziwen Gao2, Wenyan Zhu2,3
1Department of Otolaryngology-Head and Neck Surgery, The Affiliated Suzhou Hospital of Nanjing University Medical School, Suzhou, China.
概括
低氧诱导因子-1α (HIF-1α) 的激活抑制了基因素脱乙酶2 (HDAC2) 的表达,导致耐火性突然神经感应性听力损失 (SSNHL) 中的葡萄糖皮质体耐药性. HIF-1α可能预测SSNHL治疗结果.
科学领域:
- 耳鼻喉科 耳鼻喉科 耳鼻喉科
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 耐火性突发感神经听力损失 (SSNHL) 是一个重大的临床挑战.
- 了解SSNHL中葡萄糖皮质体抗性背后的分子机制对于改善治疗策略至关重要.
研究的目的:
- 研究缺氧诱导因子-1α (HIF-1α) 在耐火性SSNHL患者中的作用.
- 探索HIF-1α,基因素脱乙酶2 (HDAC2) 和葡萄皮质激素耐药性之间的关系.
主要方法:
- 三十名耐火性SSNHL患者接受了入门甲基prednisolone输液 (IMP).
- HIF-1α和HDAC2的表达被测量在周围血液单核细胞 (PBMC) 和在氧化应激下体外细胞模型中.
- 在HEI-OC1细胞中进行了基因操纵实验.
主要成果:
- 根据IMP后听力改善,患者被分为葡萄糖皮质激素敏感 (GCS) 和葡萄糖皮质激素耐药 (GCR) 组.
- 在治疗前,HDAC2的水平下降,HIF-1α在所有不耐药的SSNHL患者中增加.
- HIF-1α上调显著降低了HDAC2的表达,特别是在氧化应激下,这表明了葡萄糖皮质醇耐药性的机制.
结论:
- 似乎HIF-1α激活抑制了HDAC2的表达,从而导致耐火性SSNHL的葡萄糖皮质醇耐药性.
- HIF-1α可能作为预测耐火性SSNHL预后的潜在生物标志物.
相关概念视频
Regulation of Angiogenesis and Blood Supply
2.5K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K
Regulation of the Unfolded Protein Response
2.4K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K
Translational Regulation
1
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
1


