通过AKT信号通路,GPR83保护耳毛细胞免受伊布鲁替尼引起的听力损失
Yuhua Zhang1, Yun Xiao1, Yongjun Zhu1
1Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
Frontiers in medicine
|April 18, 2025
概括
易布鲁替尼因损害听力细胞而导致听力损失. 一种酶抑制剂 (Z-VAD-FMK) 和G蛋白结合受体83 (GPR83) 对这种耳毒性有保护作用,这表明了新的治疗策略.
科学领域:
- 耳毒性研究研究
- 癌症治疗方法 癌症治疗方法
- 细胞机制 细胞机制
背景情况:
- 易布鲁替尼是白血病药物,与听力损失有关.
- 伊布鲁丁尼布诱导的耳毒性背后的机制尚未完全理解.
研究的目的:
- 调查伊布鲁替尼的耳毒性作用.
- 阐明涉及易布鲁替尼引起的听力损失的分子途径.
- 评估潜在的防护剂,防止耳毒性.
主要方法:
- 使用细胞培养 (HEI-OC1),耳扩展剂和C57BL/6J小鼠.
- 使用听觉脑干响应 (ABR) 测试评估听力值.
- 采用RNA测序来探索分子机制,并同时使用Z-VAD-FMK来评估保护作用.
主要成果:
- 易布鲁替尼诱导了感官神经听力损失和耳毛细胞 (HC) 亡.
- 卡斯巴酶抑制剂Z-VAD-FMK通过抑制亡来减轻听力损失.
- 易布鲁替尼的耳毒性涉及蛋白激酶B和G蛋白结合受体83 (GPR83) 途径;GPR83通过自调节保护HC.
结论:
- 已证实易布鲁丁尼布具有耳毒性.
- G蛋白结合受体83 (GPR83) 在缓解易布鲁替尼引起的听力损失方面起着保护作用.
- Z-VAD-FMK和GPR83需要进一步调查,作为化学疗法诱导的耳毒性潜在干预措施.
相关概念视频
Hair Cells
39.3K
Hair cells are the sensory receptors of the auditory system—they transduce mechanical sound waves into electrical energy that the nervous system can understand. Hair cells are located in the organ of Corti within the cochlea of the inner ear, between the basilar and tectorial membranes. The actual sensory receptors are called inner hair cells. The outer hair cells serve other functions, such as sound amplification in the cochlea, and are not discussed in detail here.
39.3K
The Retinoblastoma Gene
4.0K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.0K
Inhibition of Cdk Activity
4.6K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.6K
Hearing
51.1K
When we hear a sound, our nervous system is detecting sound waves—pressure waves of mechanical energy traveling through a medium. The frequency of the wave is perceived as pitch, while the amplitude is perceived as loudness.
51.1K
PI3K/mTOR/AKT Signaling Pathway
3.3K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.3K
GPCR Desensitization
5.6K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
5.6K


