Ma Jing, Jiang Xinghao, Yarui An, Danli Jin, Xiaodie Yin, Zhang Jian, Xu Ajing
Department of Pharmacy, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai 200092, China.
School of Information Security Engineering, Shanghai JiaoTong University, 800 Jianchuan Road, Shanghai 200240, China.
Toxicol Res (Camb). 2020 Jul 13;9(4):461-466. doi: 10.1093/toxres/tfaa041. eCollection 2020 Jul.
P38 mitogen-activated protein kinase (p38 MAPK) plays an important role in innate immunity and is activated by ultraviolet (UV) radiation. However, the molecular mechanism underlying UV stress remains unclear. In this study, we reported that UV activated PMK-1/p38 MAPK signaling via JKK-1 and MOM-4 in . In , different UV radiation doses resulted in PMK-1 phosphorylation. However, pmk-1 mutants failed to demonstrate an altered survival time in response to UV when compared with wild-type worms. Further analysis showed that JKK-1, but not SEK-1 mutants, displayed impaired PMK-1 activation following UV irradiation, suggesting that JKK-1 is the upstream MAP2K for the activation of PMK-1 in under UV stimulation. UV-induced activation of PMK-1 was markedly reduced in MOM-4, but not in NSY-1 and DLK-1 mutant worms, suggesting that MOM-4 is the upstream MAP3K regulator of PMK-1 activation in response to UV stress in Additionally, daf-16 mutants displayed a shorter lifespan under UV stress, but UV-induced activation of PMK-1 was not markedly reduced in daf-16 and age-1 mutant worms. Our results revealed the signaling pathway involved in PMK-1 activation in in response to UV radiation.
P38丝裂原活化蛋白激酶（p38 MAPK）在先天免疫中起重要作用，并被紫外线（UV）辐射激活。然而，UV应激的分子机制仍不清楚。在本研究中，我们报道了在秀丽隐杆线虫中UV通过JKK-1和MOM-4激活PMK-1/p38 MAPK信号通路。在秀丽隐杆线虫中，不同剂量的UV辐射导致PMK-1磷酸化。然而，与野生型线虫相比，pmk-1突变体在UV照射下未能表现出存活时间的改变。进一步分析表明，JKK-1突变体而非SEK-1突变体在UV照射后PMK-1激活受损，这表明JKK-1是UV刺激下秀丽隐杆线虫中激活PMK-1的上游MAP2K。UV诱导的PMK-1激活在MOM-4突变体中显著降低，但在NSY-1和DLK-1突变体线虫中未降低，这表明MOM-4是秀丽隐杆线虫中响应UV应激激活PMK-1的上游MAP3K调节因子。此外，daf-16突变体在UV应激下寿命较短，但在daf-16和age-1突变体线虫中UV诱导的PMK-1激活未显著降低。我们的结果揭示了秀丽隐杆线虫中响应UV辐射激活PMK-1的信号通路。
