Bourdi Mohammed, Korrapati Midhun C, Chakraborty Mala, Yee Steven B, Pohl Lance R
Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-1760, USA.
Biochem Biophys Res Commun. 2008 Sep 12;374(1):6-10. doi: 10.1016/j.bbrc.2008.06.065. Epub 2008 Jun 27.
Recent studies in mice suggest that stress-activated c-Jun N-terminal protein kinase 2 (JNK2) plays a pathologic role in acetaminophen (APAP)-induced liver injury (AILI), a major cause of acute liver failure (ALF). In contrast, we present evidence that JNK2 can have a protective role against AILI. When male C57BL/6J wild type (WT) and JNK2(-/-) mice were treated with 300mg APAP/kg, 90% of JNK2(-/-) mice died of ALF compared to 20% of WT mice within 48h. The high susceptibility of JNK2(-/-) mice to AILI appears to be due in part to deficiencies in hepatocyte proliferation and repair. Therefore, our findings are consistent with JNK2 signaling playing a protective role in AILI and further suggest that the use of JNK inhibitors as a potential treatment for AILI, as has been recommended by other investigators, should be reconsidered.
最近在小鼠身上进行的研究表明，应激激活的c-Jun氨基末端蛋白激酶2（JNK2）在对乙酰氨基酚（APAP）诱导的肝损伤（AILI）中起病理作用，而AILI是急性肝衰竭（ALF）的主要原因。相比之下，我们提供的证据表明JNK2对AILI具有保护作用。当雄性C57BL/6J野生型（WT）和JNK2基因敲除（-/-）小鼠接受300mg APAP/kg处理时，48小时内90%的JNK2（-/-）小鼠死于ALF，而WT小鼠的死亡率为20%。JNK2（-/-）小鼠对AILI的高易感性似乎部分归因于肝细胞增殖和修复的缺陷。因此，我们的研究结果与JNK2信号在AILI中起保护作用一致，并且进一步表明，正如其他研究人员所建议的，将JNK抑制剂用作AILI的潜在治疗方法应重新考虑。
