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在高血糖-缺血条件下,内皮细胞的核因子-卡帕B (NF-κB) 信号通路中的新组件

Madhu V Singh¹, Thomas Wong¹, Sonia Moorjani¹

¹Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City, IA, United States.

Frontiers in cardiovascular medicine

|June 10, 2024

概括

糖尿病通过破坏核因子-卡帕B (NF-κB) 信号传递,损害了外周动脉疾病 (PAD) 的恢复. 这项研究确定BLNK/BTK是内皮细胞的关键上游调节器,为改善糖尿病患者缺血适应提供了一个新的目标.

科学领域:

内皮细胞生物学内皮细胞生物学
分子信号通道的分子信号通道.
血管疾病机制血管疾病机制

背景情况:

糖尿病会加剧血管疾病,如外周动脉疾病 (PAD),部分是通过慢性炎症.
核因子-kappa B (NF-κB) 激活对于实验性PAD的恢复至关重要.
过高血糖会损害通过蛋白激酶Cββ (PKCβ) 的缺血诱导的规范NF-κB通路激活.

研究的目的:

在缺血条件下阐明高血糖对内皮细胞中正规和非正规NF-κB通路信号传递的影响.
为了识别PKCβ上游的信号分子,参与高血糖引起的NF-κB激活损伤.

主要方法:

使用的内皮细胞暴露于高血糖和缺血症 (HGI).
采用抗体阵列来评估约100种蛋白质的酸化.
使用生物信息学工具进行途径分析,并对已识别的标进行药理抑制.

主要成果:

在HGI条件下确定了蛋白质酸化的变化.
途径分析表明,布鲁顿的氨酸激酶 (BTK) 和B细胞链接蛋白 (BLNK) 参与了观察到的信号变化.
抑制BLNK/BTK减弱了PKC激活,并在HGI治疗的内皮细胞中恢复了IκBα降解.

结论:

在高血糖期间,BLNK/BTK信号传递是PKCβ在内皮细胞上游的关键组成部分.
这一途径有助于在高血糖症中观察到的受损的正规NF-κB激活.
针对BLNK/BTK可能提供一种治疗策略,以改善糖尿病血管并发症的后缺血适应.

关键词:

在 BLNK/BTK 中.在 NF-κBB 中.糖尿病糖尿病患者糖尿病患者它们是内皮细胞的内皮细胞.过高血糖症 (hyperglycemia) 是一种这是一种炎症炎症炎症炎症.周围动脉疾病是什么蛋白质激酶 C 的蛋白质激酶 C.

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