Melatonin alleviates lipopolysaccharide-induced placental cellular stress response in mice
Abstract: It has been demonstrated that melatonin protected mice from lipopolysaccharide (LPS)-induced fetal death and intra- uterine growth retardation. Nevertheless, its molecular mechanism remains obscure. In the present study, we investigated the effects of melatonin on LPS-induced cellular stress in placenta. The pregnant mice were administered with melatonin ”5.0 mg/kg, intraperitoneal (I.p.)” 30 min before and 150 min after LPS (300 μg/kg, I.p.) on gestational day 15. Oxidative stress, endoplasmic reticulum (ER) stress, hypoxic stress and heat stress in placenta were analyzed at 4 h after LPS. As expected, maternal LPS administration resulted in placental GSH depletion and up-regulated the expression of placental antioxidative enzymes. In addition, LPS significantly increased the level of inducible nitric oxide synthase (Inos) and enhanced the intensity of placental 3- nitrotyrosine (3-NT) residues. An ER stress, as determined by a decreased GRP78 expression, an obvious eIF2a and JNK phosphorylation, and an increased CHOP expression, were observed in placenta of pregnant mice injected with LPS. In addition, LPS significantly increased Mrna level of placental HIF-1a, VEGF and ET-1, the markers of hypoxic stress. Heme oxygenase (HO)-1, a marker of heat stress, was also up-regulated in placenta of LPS-administered pregnant mice. Interestingly, LPS-induced placental oxidative stress, hypoxic stress and ER stress were significantly alleviated when pregnant mice were administered with melatonin, whereas melatonin had little effect on LPS-evoked placental HO-1 expression. In conclusion, maternally administered melatonin alleviates LPS-induced cellular stress in placenta. Melatonin may be used as pharmacological agents to protect the fetuses against LPS-induced intra-uterine fetal death and intra-uterine growth restriction.
oxidative stress, endoplasmic reticulum stress, hypoxic stress, heat stress,melatonin, lipopolysaccharide placenta
Hua Wang Ling Li Mei Zhao Yuan-Hua Chen Zhi-Hui Zhang Cheng Zhang Yan-Li Ji Xiu-Hong Meng De-Xiang Xu
Department of Toxicology, School of public health, Anhui Medical University, Hefei 230032
国内会议
合肥
英文
78-96
2011-08-10（万方平台首次上网日期，不代表论文的发表时间）