Institute of Animal Husbandry and Veterinary, Tibet Autonomous Regional Academy of Agricultural Sciences, Tibet, China.
Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Tibet, China.
Anim Biotechnol. 2024 Nov;35(1):2299241. doi: 10.1080/10495398.2023.2299241. Epub 2024 Jan 4.
Hypoxia is an important characteristic of Tibetan plateau environment. It can lead to apoptosis, but the mechanism of apoptosis caused by hypoxic stress needs further clarification. Here, cattle kidney cell MDBK were used as cell model. The effect of hypoxic stress on apoptosis and its molecular mechanism were explored. MDBK cells were treated with hypoxic stress, apoptosis and mitochondrial apoptotic pathway were significantly increased, and the expression of B-cell lymphoma 6 (BCL6) was significantly decreased. Overexpressing or inhibiting BCL6 demonstrated that BCL6 inhibited the apoptosis. And the increase of apoptosis controlled by hypoxic stress was blocked by BCL6 overexpressing. MDBK cells were treated with hypoxic stress, the expression and the nuclear localization of p53 were significantly increased. Overexpressing or inhibiting p53 demonstrated that hypoxic stress suppressed the expression of BCL6 through p53. Together, these results indicated that hypoxic stress induced the apoptosis of MDBK cells, and BCL6 was an important negative factor for this regulation process. In MDBK cells, hypoxic stress suppressed the expression of BCL6 through p53/BCL6-mitochondrial apoptotic pathway. This study enhanced current understanding of the molecular mechanisms underlying the regulation of apoptosis by hypoxic stress in MDBK cells.
低氧是青藏高原环境的一个重要特征。它可以导致细胞凋亡，但低氧应激引起凋亡的机制还需要进一步阐明。在这里，我们以牛肾细胞 MDBK 作为细胞模型，探讨了低氧应激对细胞凋亡及其分子机制的影响。用低氧应激处理 MDBK 细胞，细胞凋亡和线粒体凋亡途径明显增加，B 细胞淋巴瘤 6（BCL6）的表达明显降低。过表达或抑制 BCL6 表明 BCL6 抑制了细胞凋亡。并且由低氧应激控制的细胞凋亡增加被 BCL6 过表达所阻断。用低氧应激处理 MDBK 细胞，p53 的表达和核定位明显增加。过表达或抑制 p53 表明，p53 通过 BCL6/线粒体凋亡途径抑制 BCL6 的表达。综上所述，这些结果表明，低氧应激诱导了 MDBK 细胞的凋亡，BCL6 是这一调节过程的一个重要负性因子。在 MDBK 细胞中，低氧应激通过 p53/BCL6-线粒体凋亡途径抑制 BCL6 的表达。本研究增强了对 MDBK 细胞中低氧应激调节细胞凋亡的分子机制的理解。
