Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, USA.
Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, USA; Division of Pulmonary and Critical Care Medicine, Albany Medical College, Albany, NY, USA.
Redox Biol. 2023 Sep;65:102838. doi: 10.1016/j.redox.2023.102838. Epub 2023 Aug 9.
Identifying novel regulators of vascular smooth muscle cell function is necessary to further understand cardiovascular diseases. We previously identified cytoglobin, a hemoglobin homolog, with myogenic and cytoprotective roles in the vasculature. The specific mechanism of action of cytoglobin is unclear but does not seem to be related to oxygen transport or storage like hemoglobin. Herein, transcriptomic profiling of injured carotid arteries in cytoglobin global knockout mice revealed that cytoglobin deletion accelerated the loss of contractile genes and increased DNA damage. Overall, we show that cytoglobin is actively translocated into the nucleus of vascular smooth muscle cells through a redox signal driven by NOX4. We demonstrate that nuclear cytoglobin heterodimerizes with the non-histone chromatin structural protein HMGB2. Our results are consistent with a previously unknown function by which a non-erythrocytic hemoglobin inhibits DNA damage and regulates gene programs in the vasculature by modulating the genome-wide binding of HMGB2.
确定血管平滑肌细胞功能的新型调节因子对于进一步了解心血管疾病是必要的。我们之前已经鉴定出细胞球蛋白，一种肌球蛋白和细胞保护作用的血红蛋白同源物在脉管系统中。细胞球蛋白的具体作用机制尚不清楚，但似乎与血红蛋白的氧气运输或储存无关。在此，对细胞球蛋白全局敲除小鼠损伤颈动脉的转录组分析表明，细胞球蛋白缺失加速了收缩基因的丧失，并增加了 DNA 损伤。总的来说，我们表明细胞球蛋白通过由 NOX4 驱动的氧化还原信号主动转位到血管平滑肌细胞核中。我们证明核细胞球蛋白与非组蛋白染色质结构蛋白 HMGB2 异二聚化。我们的结果与一个以前未知的功能一致，即非红细胞血红蛋白通过调节 HMGB2 的全基因组结合来抑制 DNA 损伤并调节血管中的基因程序。
