【摘 要】
：
Acetaminophen(APAP)overdose induces apoptosis-inducing factor(AIF)-dependent necroptosis,but the mechanism remains obscure.The present study investigated the role of receptor interacting protein(RIP)1
【机 构】
：
Department of Toxicology,Anhui Medical University,Hefei,China
【出 处】
：
中华预防医学会自由基预防学专业委员会2014年学术交流会议
论文部分内容阅读
Acetaminophen(APAP)overdose induces apoptosis-inducing factor(AIF)-dependent necroptosis,but the mechanism remains obscure.The present study investigated the role of receptor interacting protein(RIP)1,a critical mediator of necroptosis,on AIF-dependent necroptosis during APAP-induced acute liver failure.Mice were intraperitoneally injected with APAP(300 mg/kg).As expected,hepatic RIP1 was activated as early as 1 h after APAP,which is earlier than APAP-induced hepatic RIP3 upregulation.APAP-evoked RIP1 activation is associated with hepatic glutathione(GSH)depletion.Either pretreatment or post-treatment with Nec-1,a selective inhibitor of RIP1,significantly alleviated APAP-induced acute liver failure.Moreover,Nec-1 improved the survival and prevented APAP-induced necroptosis,as determined by TdT-mediated dUTP-biotin nick end labeling(TUNEL)assay.Further analysis showed that Nec-1 significantly inhibited APAP-induced hepatic c-Jun N-terminal kinase(JNK)phosphorylation and mitochondrial Bax translocation.In addition,Nec-1 blocked APAP-induced translocation of AIF from the mitochondria to the nucleus.Of interest,no changes were induced by Nec-1 on hepatic CYP2E1 expression.In addition,Nec-1 had little effect on APAP-induced hepatic GSH depletion at early stage.Taken together,these results suggest that RIP1 is involved in APAP-induced necroptosis.Nec-1 is an effective antidote for APAP-induced acute liver failure.
其他文献
目的 应用血管回声跟踪技术(echo-tracking,ET)对终末期肾脏病(end-stage renal disease,ESRD)患者的颈总动脉及桡动脉弹性进行评价,初步判定ESRD患者动脉硬化的灵敏指标,并且确定诊断ESRD患者动脉硬化的截断值。方法 应用ET技术检测34例ESRD患者颈总动脉及桡动脉弹性参数,并与30例健康正常人的动脉弹性参数进行分析比较,初步确定ESRD患者动脉硬化ET
肾脏是调节人体血磷平衡的重要器官,肾功能下降时,肾脏对磷的排泄功能降低,导致血磷水平逐渐升高;肾功能下降时,近曲小管产生骨化三醇减少,致低钙血症和骨代谢异常的发生.血磷升高促进继发性甲状旁腺功能亢进、加重体内钙磷代谢紊乱、促进血管钙化,最终导致肾衰患者死亡率增加.我国针对透析患者进行的矿物质和骨代谢异常的多中心研究显示:维持性血液透析患者血钙、血磷、血iPTH水平不达标的比例分别为:42 ％、57
Objective To investigate the clavicular hook plate of the Zimmer self- lock wire- rope compared the clinical analysis of efficacy in the treatment of acromioclavicular joint dislocation and evaluation
Objective Through the development of "construction management in Department of surgery ward thrombosis" joint,thrombus prevention standard vein,reduce Department of orthopedics after operation for ven
Department of Orthopaedics,The First Affiliated Hospital of China Medical University,Shenyang City,Liaoning 110001,China Objective Our research is to transplant temporary tumorigenesis bone marrow mes
Objective To evaluate the potential protective effects of extracts from fructus rhodomyrti(FR)against oxidative DNA damage using a cellular system,and the antioxidant ability on potassium bromate(KBrO
It is increasingly recognized that intra-uterine growth restriction(IUGR)is associated with an increased risk of metabolic disorders in late life.Previous studies showed that mice exposed to LPS in la
Several earlier reports demonstrated that maternal zinc deficiency during pregnancy was linked with adverse pregnant outcomes.Nevertheless,it needs to be determined whether maternal zinc deficiency du
Several studies demonstrated that vitamin D status was negatively correlated with acute kidney injury in critically ill patients.In the present study,we investigated the effects of oral supplementatio
Several reports demonstrated that mice exposed to LPS at middle gestational stage caused neural tube defects(NTDs).The present study investigated the effects of vitamin D3 supplementation on LPS-induc