The response of AMP-activated protein kinase (AMPK) to oxidative stress has been recently reported but the downstream signals this are largely unknown. Meanwhile, upstream events for activation nuclear factor erythroid-2-related factor-2 (Nrf2), a critical transcriptional activator antioxidative responses, remain unclear. In present study, we investigated relationship between AMPK and Nrf2 signal pathways in lipopolysaccharide (LPS)-triggered inflammatory system, which berberine (BBR), known...

Transcription factor NF-E2-related 2 (Nrf2) regulates the induction of antioxidative proteins, including heme oxygenase-1 (HO-1). Nrf2 is sequestered in cytoplasm by Keap1 under unstimulated conditions but translocates into nucleus and transactivates antioxidant responsive element (ARE) upon exposure to oxidative insults. It has recently been demonstrated that vitro phosphorylation on Ser40 protein kinase C (PKC) facilitates dissociation from complex (Huang HC, Nguyen T, Pickett CB. J Biol...

We used lipopolysaccharide (LPS) to activate microglia that play an important role in the brain immune system. LPS injected into rat hippocampus CA1 region activated microglial cells resulting increased production of interleukin (IL)-1β and tumor necrosis factor (TNF)-α during initial stage treatment. Immunostaining for IL-1β was at 6 hr after injection. IL-1β-immunopositive were co-localized with immunostaining CD11b. Subacute treatment by same route 5 days caused long-term activation...

Parkinson's disease (PD) is an age-related progressive neurodegenerative disorder caused by selective loss of dopaminergic neurons from the substantia nigra (SN) to striatum. The initial factor that triggers neurodegeneration unknown; however, inflammation has been demonstrated be significantly involved in progression PD. present study was designed investigate role pro-inflammatory cytokine interleukin-1 (IL-1) activation microglia and decline motor function using IL-1 knockout (KO)...

Objective— Reactive oxygen species are important mediators for platelet-derived growth factor (PDGF) signaling in vascular smooth muscle cells, whereas excess reactive species–induced oxidative stress contributes to the development and progression of diseases, such as atherosclerosis. Activation redox-sensitive transcription factor, nuclear erythroid 2-related 2 (Nrf2), is pivotal cellular defense against by transcriptional upregulation antioxidant proteins. This study aimed elucidate role...

1-phenyl-2-(1-pyrrolidinyl)-1-pentanone (α-PVP) is a new designer drug of the cathinone type. People who have taken drugs containing α-PVP or other synthetic reportedly lose consciousness, develop difficulty breathing, and at worst case, die. However, mechanism underlying α-PVP-induced neurotoxicity unknown. The objective present study was to investigate effect on central nervous system (CNS) compare its with that methamphetamine (METH) in mice. Balb/c male mice (8 weeks old) were orally...

Abstract Background Cyclooxygenase-2 (COX-2) is induced in inflammatory cells response to cytokines and pro-inflammatory molecules, suggesting that COX-2 has a role the process. The objective of current study was examine whether celecoxib, selective inhibitor, could ameliorate lipopolysaccharide (LPS)-induced brain inflammation, dopaminergic neuronal dysfunction sensorimotor behavioral impairments. Methods Intraperitoneal (i.p.) injection LPS (2 mg/kg) performed rat pups on postnatal Day 5...

Abstract Abnormal increases in vascular smooth muscle cells (VSMCs) the intimal region after a injury is key event developing neointimal hyperplasia. To maintain function, proliferation and apoptosis of VSMCs tightly controlled during remodeling. NF-E2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) system, component oxidative stress response that acts maintaining homeostasis, plays an important role hyperplasia injury; however, Nrf2/Keap1 VSMC has not been clarified....

BACKGROUND Most species of aconite contain highly toxic aconitines, the oral ingestion which can be fatal, primarily because they cause ventricular arrhythmias. We describe a case severe poisoning that was successfully treated through veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and in detailed toxicological analyses roots biological samples were performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). CASE SUMMARY A 23-year-old male presented to emergency...

Aconitum poisoning can cause severe arrhythmias. We report, for the first time, detailed blood and urine concentrations of four aconitine alkaloids in a male patient his 20s who ingested aconite roots with suicidal intent. The developed refractory torsade de pointes (TdP) required veno-arterial extracorporeal membrane oxygenation. His TdP resolved 7 h after arrival, sinus rhythm returning within 12 h. was discharged 6 days later. Subsequent measurements over time showed that jesaconitine had...

Phorone, a glutathione (GSH) depletor, induces the expression of mRNAs heme oxygenase-1 (HO-1) and c-jun by mediating activation activated protein-1 (AP-1) in rat livers. We have shown that phorone activates c-Jun N-terminal kinase (JNK), thus leading to phosphorylation, transactivation AP-1 HO-1 gene liver response oxidative stress. The in-gel assay showed JNK1 predominantly nuclear extract. JNK was slightly observed at 1 hr after administration gradually increased with time....

CAR (constitutive androstane receptor) is a nuclear receptor that regulates the transcription of target genes, including CYP (cytochrome P450) 2B and 3A. The transactivation by regulated its subcellular localization; however, mechanism governs translocation has yet to be clarified. It been reported recently AMPK (AMP-activated protein kinase) involved in phenobarbital-mediated CYP2B induction particular culture system. We therefore investigated vivo whether activation CAR-dependent gene...

Abstract Human leukemia K562 cell differentiation induction by naturally occurring bufadienolides purified from the Chinese drug Senso and synthetic bufalin derivatives was examined a nitro blue tetrazolium reduction assay. Bufalin showed strongest activity among all tested in this study. The degree of diformazan positive cells correlated well with their inhibitory activities against Na + , K ‐ATPase prepared vitro. N ‐ATPases variant clone (ouabain resistant, OuaR) murine line M1‐T22, which...

Abstract: Certain chemotherapeutic agents subject cells to oxidative stress, thereby promoting adverse effects. However, the molecular machinery governing 5-fluorouracil (5-FU)-mediated myelotoxicity is obscure. The purpose of this study was clarify whether 5-FU-induced a cause stress. Treatment mice with 5-FU (75 mg/kg, i.p.) caused significant induction haem oxygenase-1 and decrease in glutathione contents bone marrow cells, both which are indicators 5-FU-mediated myeloid colony formation...

Constitutive androstane receptor (CAR) is a nuclear that regulates the transcription of target genes, including CYP2B and 3A. Phenobarbital activates CAR, at least in part, an AMP-activated protein kinase (AMPK)-dependent manner. However, precise mechanisms underlying phenobarbital activation AMPK are still unclear. In present study, it was demonstrated administration to mice decreases hepatic miR-122, liver-enriched microRNA involved both differentiation function. The time-course change...

Abstract We have developed an animal model of learning and memory impairment associated with activation microglia in the mouse brain. Injection lipopolysaccharide into CA1 region hippocampus resulted increased production inflammatory cytokines, such as interleukin‐1β. Immunostaining for interleukin‐1β revealed increase signal at 6 hr after injection. Immunopositive cells were colocalized those immunopositive CD11b. When subacute treatment (20 μg/2 μl/injection, bilaterally 5 consecutive...

Endogenously produced reactive oxygen species reportedly stimulate insulin secretion from islet β-cells. However, the molecular machinery that governs oxidant-induced has yet to be determined. The present study demonstrates, using rat β-cell-derived RINm5F cells, involvement of transient receptor potential (TRP) cation channels in induced by lipid peroxidation product 4-hydroxy-2-nonenal. Short-term (1 h) exposure 4-hydroxy-2-nonenal a increase intracellular Ca2+ concentration and subsequent...