Department of Cadre Health Care, Qingdao Municipal Hospital, Qingdao, Shandong, China.
Eur Rev Med Pharmacol Sci. 2017 Aug;21(16):3674-3679.
Mitochondria are abundant in liver. The roles of mitochondrial protein in liver injury and related signaling pathways are still unclear. UCP1 is a novel mitochondrial transmembrane protein. Its expression pattern and function in liver still needs further investigation.
A mouse model of liver injury was established by the treatment of LPS. UCP1 expression in the liver tissue was detected by Western blot and qRT-PCR. ERK signaling activity was tested by enzymatic activity kit. ATP production was evaluated by flow cytometry. Cell apoptosis was determined by Western blot and flow cytometry. ERK signaling pathway inhibitor, U0126, was used to pre-treat mice. Liver tissue from sepsis patients was collected from the surgery.
Our data showed that the level of UCP1 was upregulated, ERK signaling was activated, ATP production was reduced, and cell apoptosis was enhanced in mice with liver injury model caused by LPS. U0126 intervention significantly suppressed UCP1 expression, inhibited ERK signaling pathway, enhanced ATP production, and restrained liver cell apoptosis in mice liver injury model. UCP1 increased, ERK signaling activated, and cell apoptosis elevated in the liver tissue of sepsis patients.
UCP1 plays a role in the liver tissue of mouse liver injury model and sepsis patients through the modulation of mitochondrial ATP production and cell apoptosis by ERK signaling pathway.
线粒体在肝脏中含量丰富。线粒体蛋白在肝损伤及相关信号通路中的作用尚不清楚。UCP1 是一种新型的线粒体跨膜蛋白。其在肝脏中的表达模式和功能仍需进一步研究。
采用 LPS 处理建立小鼠肝损伤模型，通过 Western blot 和 qRT-PCR 检测肝组织中 UCP1 的表达，通过酶活性试剂盒检测 ERK 信号活性，通过流式细胞术评估 ATP 产生，通过 Western blot 和流式细胞术检测细胞凋亡。用 ERK 信号通路抑制剂 U0126 预处理小鼠。从手术中收集脓毒症患者的肝组织。
我们的数据表明，在 LPS 引起的肝损伤模型小鼠中，UCP1 水平上调，ERK 信号被激活，ATP 产生减少，细胞凋亡增强。U0126 干预显著抑制了 UCP1 的表达，抑制了 ERK 信号通路，增强了 ATP 的产生，并抑制了肝损伤模型中小鼠的肝细胞凋亡。在脓毒症患者的肝组织中，UCP1 增加，ERK 信号被激活，细胞凋亡增加。
UCP1 通过 ERK 信号通路调节线粒体 ATP 产生和细胞凋亡，在小鼠肝损伤模型和脓毒症患者的肝脏组织中发挥作用。
