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Enzyme
Compound
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Target Concepts:
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Query: UNIPROT:P05412 (
c-Jun
)
11,453
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Neurodegenerative disorders are characterized by progressive degeneration and loss of neurons in the brain. Oxidative stress is implicated in the pathogenesis of neurological disorders, although the pathological mechanism remains unelucidated.
Daphnetin
, an active ingredient extracted from
Changbai daphne
(Daphne Korean Nakai), exhibits various pharmacological effects, including anti-inflammatory, anti-oxidative and anti-tumor effects. However, the neuroprotective effects, as well as the specific mechanisms of daphnetin, remain unclear. Neuronal-like rat pheochromocytoma PC12 cells were pretreated with daphnetin for 2 h, then treated with or without H
2
O
2
for various times. Cell morphology was detected using an inverted microscope, the apoptotic ratio was determined by Annexin V fluorescein isothiocyanate/propidium iodide assay, nuclear morphology was observed and photographed using a fluorescence microscope following 4',6-diamidino-2-phenylindole staining. The levels of pro-caspase 3, cleavage of poly ADP-ribose polymerase and caspase 3 were detected by western blotting. In addition, the activation of mitogen-activated protein kinase (MAPK) signal pathway and the expression of HSP70 were detected by western blotting. The present study demonstrated that daphnetin attenuated hydrogen peroxide (H
2
O
2
)-induced apoptosis in a concentration-dependent manner, reduced the cleavage of poly ADP ribose polymerase and caspase 3, and inhibited the phosphorylation of p38 MAPK and
c-Jun
N-terminal kinases (JNK) in H
2
O
2
-induced PC12 cells. In addition, daphnetin induced the expression of HSP70 in a dose- and time-dependent manner, and daphnetin-induced HSP70 expression was reduced by extracellular signal-regulated kinase (ERK) 1/2 inhibitor U0126 in PC12 cells. Therefore, the present results indicate that daphnetin protects PC12 cells against oxidative stress injury by regulating p38 MAPK and JNK signaling and increasing the expression of HSP70 via ERK signaling. This suggests that daphnetin may have the potential to treat certain neurodegenerative diseases. The present results not only provide insight into the potential use of daphnetin in H
2
O
2
-induced PC12 cell apoptosis, but also highlight the potential role of HSP70 in neuroprotection.
...
PMID:Daphnetin protects oxidative stress-induced neuronal apoptosis via regulation of MAPK signaling and HSP70 expression. 2758 45
Daphnetin
(Daph), a natural coumarin derivative isolated from plants of the Genus Daphne, possesses abundant biological activities, such as anti-inflammatory, antioxidant and anticancer properties. In the present study, we focused on investigating the protective effect of Daph against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage, mitochondrial dysfunction and the involvement of underlying molecular mechanisms. Our findings indicated that Daph effectively inhibited t-BHP-stimulated cytotoxicity, cell apoptosis, and mitochondrial dysfunction, which are associated with suppressed reactive oxygen species (ROS) generation, decreased malondialdehyde (MDA) formation, increased superoxide dismutase (SOD) levels and glutathione (GSH)/GSSG (oxidized GSH) ratio. Further investigation indicated that Daph significantly suppressed cytochrome c release and NLRP3 inflammasome activation and modulated apoptosis-related protein Bcl-2, Bax, and caspase-3 expression. Moreover, Daph dramatically induced the expression of the glutamate-cysteine ligase modifier (GCLM) subunit and the glutamate-cysteine ligase catalytic (GCLC) subunit, heme oxygenase-1 (HO-1), and NAD (P) H: quinone oxidoreductase (NQO1), which is largely dependent on upregulating the nuclear factor-erythroid 2-related factor 2 (Nrf2) nuclear translocation, reducing the Keap1 protein expression, and strengthening the antioxidant response element (ARE) promoter activity. Additionally, Daph remarkably activated a
c-Jun
NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) phosphorylation, but ERK and JNK inhibitor pretreatment exhibited an evident decrease of the level of Daph-enhanced Nrf2 nuclear translocation. Furthermore, Daph exposure suppressed t-BHP-induced cytotoxicity and ROS overproduction, which are mostly blocked in Nrf2 knockout RAW 264.7 cells and peritoneal macrophages. Accordingly, Daph exhibited protective roles against t-BHP-triggered oxidative damage and mitochondrial dysfunction by the upregulation of Nrf2 antioxidant signaling pathways, which may be involved in the activation of JNK and ERK.
...
PMID:Daphnetin-mediated Nrf2 antioxidant signaling pathways ameliorate tert-butyl hydroperoxide (t-BHP)-induced mitochondrial dysfunction and cell death. 2818 24
NF-E2 p45-related factor 2 (Nrf2), which regulates the cellular antioxidant response, is a target for limiting tissue damage due to exposure to environmental toxicants, including arsenic.
Daphnetin
(Daph), a natural coumarin derivative, has been shown to induce remarkable antioxidant activity. The present study aimed to examine the protective effects and molecular mechanisms of Daph on arsenic-induced cytotoxicity in human lung epithelial cells. Our results demonstrate that Daph dramatically upregulated the antioxidant enzyme in a dose dependent manner, in association with induction of Nrf2 nuclear translocation and decreased Keap1 protein expression. Importantly, Daph also markedly induced the activation of AMP-activated protein kinase (AMPK),
c-Jun
NH
2
-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) phosphorylation. Furthermore, Daph antagonized the arsenic-induced decreases in cell viability and the generation of reactive oxygen species (ROS). Notably, Daph pretreatment reversed the arsenic-induced decrease in anti-apoptotic factor B-cell lymphoma-2 (Bcl-2) and the increase in pro-apoptotic factor Bcl-2-associated X protein (Bax). The effects of Daph on Nrf2 and HO-1 activation, and arsenic-induced cell viability were largely weakened when Nrf2 was depleted in vitro. Accordingly, Daph might ameliorate arsenic-induced cytotoxicity and apoptosis, which may be linked to the induction of Nrf2-dependent antioxidant responses as well as stabilization of the anti-apoptotic factor Bcl-2 in human lung epithelial cells.
...
PMID:Daphnetin activates the Nrf2-dependent antioxidant response to prevent arsenic-induced oxidative insult in human lung epithelial cells. 3073 23
