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Search results for: JNK2 (dn)

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#21863240   2011/08/24 To Up

Impact of JNK1, JNK2, and ligase Itch on reactive oxygen species formation and survival of prostate cancer cells treated with diallyl trisulfide.

In our previous study, we demonstrated that diallyl trisulfide (DATS) induced iron-dependent G2-M arrest of prostate cancer cell cycle. Moreover, ferritin degradation and an increase of labile iron pool has been linked to the activation of the JNK signaling axis. In the present work, we extended this study to determine which of the c-jun kinases is responsible for ferritin degradation and the role of iron in DATS-induced cell death. We hypothesized that JNK1 activates Itch ligase which will lead to ferritin ubiquitination, an increase in iron-dependent ROS formation and cell death.
Alicja Sielicka-Dudzin, Andzelika Borkowska, Anna Herman-Antosiewicz, Michal Wozniak, Agnieszka Jozwik, Donatella Fedeli, Jedrzej Antosiewicz

1773 related Products with: Impact of JNK1, JNK2, and ligase Itch on reactive oxygen species formation and survival of prostate cancer cells treated with diallyl trisulfide.

50 ug 96T96T50 ug 50 ug 100ul

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#21554942   2011/05/01 To Up

Activity of all JNK isoforms contributes to neurite growth in spiral ganglion neurons.

Jun N-terminal kinase (JNK) is a multifunctional protein kinase crucial for neuronal apoptosis as well as neurite growth. We have previously shown that JNK activity is correlated with spiral ganglion neuron (SGN) apoptosis following hair cell loss in rats (Alam et al., 2007) implying that JNK inhibition may have therapeutic potential to protect SGNs in deaf individuals. Here we investigated the role of JNK in neurite outgrowth from cultured neonatal rat and mouse SGNs. We show that JNK is required for initial growth of neurites and for continued extension of already established neurites. The effect of JNK inhibition on neurite growth is rapid and is also rapidly reversible after washout of the inhibitor. Using phosphoJNK immunoreactivity as an indicator, we show that JNK is activated in growth cones within 30 min after transfer to medium lacking neurotrophic stimuli (5 K medium) but activation in the nucleus and soma requires hours. By transfecting epitope-tagged JNK1, JNK2, or JNK3 isoforms into SGNs, we found that all are present in the nucleus and cytoplasm and that there is no preferential redistribution to the nucleus after transfer to 5 K medium. Cotransfection of dominant-negative (dn) JNK1 and JNK2 into SGNs reduced neurite growth, although transfection of dnJNK1 or dnJNK2 alone had no significant effect. SGNs cultured from JNK3(-/-) mice showed reduced neurite growth that was further reduced by transfection of dnJNK1 and dnJNK2. This indicates that all three JNK isoforms promote SGN neurite growth although there may be functional redundancy between JNK1 and JNK2.
Patrick J Atkinson, Chang-Hyun Cho, Marlan R Hansen, Steven H Green

1078 related Products with: Activity of all JNK isoforms contributes to neurite growth in spiral ganglion neurons.

1 kit1 kit96 assays 0.1 mg1 kit(96 Wells)1 mg100.00 ug100 48 assays

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#21270260   // To Up

Selective inactivation of c-Jun NH2-terminal kinase in adipose tissue protects against diet-induced obesity and improves insulin sensitivity in both liver and skeletal muscle in mice.

Obesity is associated with increased activation of the c-Jun NH(2)-terminal kinase (JNK) in several metabolic organs, including adipose tissue, liver, and skeletal muscle. In this study, we aimed to define the role of JNK activation in adipose tissue in the development of obesity-related insulin resistance.
Xinmei Zhang, Aimin Xu, Sookja K Chung, Justin H B Cresser, Gary Sweeney, Rachel L C Wong, Anning Lin, Karen S L Lam

1863 related Products with: Selective inactivation of c-Jun NH2-terminal kinase in adipose tissue protects against diet-induced obesity and improves insulin sensitivity in both liver and skeletal muscle in mice.

96 wells

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#19837872   2009/10/16 To Up

Forkhead box O1/pancreatic and duodenal homeobox 1 intracellular translocation is regulated by c-Jun N-terminal kinase and involved in prostaglandin E2-induced pancreatic beta-cell dysfunction.

Prostaglandin E(2) (PGE(2)) is a well-known mediator of beta-cell dysfunction in both type 1 and type 2 diabetes. We recently reported that down-regulation of the Akt pathway activity is implicated in PGE(2)-induced pancreatic beta-cell dysfunction. The aim of this study was to further dissect the signaling pathway of this process in pancreatic beta-cell line HIT-T15 cells and primary mouse islets. We found that PGE(2) time-dependently increased the c-Jun N-terminal kinase (JNK) pathway activity. JNK inhibition by the JNK-specific inhibitor SP600125 reversed PGE(2)-inhibited glucose-stimulated insulin secretion (GSIS). PGE(2) induced dephosphorylation of Akt and FOXO1, leading to nuclear localization and transactivation of FOXO1. Activation of FOXO1 induced nuclear exclusion but had no obvious effect on the whole-cell protein level of pancreatic and duodenal homeobox 1 (PDX1). However, these effects were all attenuated by JNK inhibition. Furthermore, adenovirus-mediated overexpression of dominant-negative (DN)-FOXO1 abolished whereas constitutively active (CA)-FOXO1 mimicked the effects of PGE(2) on GSIS in isolated mouse islets. In addition, we demonstrated that DN-JNK1 but not DN-JNK2 or CA-Akt abolished the PGE(2)-induced AP-1 luciferase reporter activity, whereas DN-JNK1 and CA-Akt but not DN-JNK2 reversed the effect of PGE(2) on FOXO1 transcriptional activity, and overexpression of DN-JNK1 rescued PGE(2)-impaired GSIS in mouse islets. Our results revealed that activation of the JNK is involved in PGE(2)-induced beta-cell dysfunction. PGE(2)-mediated JNK1 activation, through dephosphorylation of Akt and FOXO1, leads to nuclear accumulation of FOXO1 and nucleocytoplasmic shuttling of PDX1, finally resulting in defective GSIS in pancreatic beta-cells.
Zhuoxian Meng, Jinghuan Lv, Ying Luo, Yan Lin, Yunxia Zhu, Jia Nie, Tao Yang, Yujie Sun, Xiao Han

1544 related Products with: Forkhead box O1/pancreatic and duodenal homeobox 1 intracellular translocation is regulated by c-Jun N-terminal kinase and involved in prostaglandin E2-induced pancreatic beta-cell dysfunction.

100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized

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#16627484   2006/04/19 To Up

c-Jun N-terminal kinase-mediated stabilization of microsomal prostaglandin E2 synthase-1 mRNA regulates delayed microsomal prostaglandin E2 synthase-1 expression and prostaglandin E2 biosynthesis by cardiomyocytes.

Microsomal prostaglandin (PG) E(2) synthase-1 (mPGES-1) catalyzes the terminal step in the biosynthesis of PGE(2), a key proinflammatory mediator. The purpose of this study was to elucidate the regulation of mPGES-1 mRNA expression in cardiomyocytes, define the role of JNK enzymes in this process, and characterize the role of mPGES-1 in cardiomyocyte PGE(2) biosynthesis. In neonatal cardiomyocytes, interleukin-1beta and lipopolysaccharide (LPS) both stimulated mPGES-1 mRNA expression and increased mPGES-1 mRNA stability and protein synthesis but failed to increase mPGES-1 mRNA transcription. Treatment with the JNK1/2 inhibitor, SP600125, abrogated the increases in mPGES-1 mRNA stability, mPGES-1 protein synthesis, and PGE(2) release induced by interleukin-1beta or LPS. mPGES-1 protein synthesis was observed in LPS-stimulated neonatal cardiomyocytes from jnk1(-/-) or jnk2(-/-) mice. In contrast, infection of jnk1(-/-) cardiomyocytes with an adenovirus encoding phosphorylation-resistant JNK2 (ad-JNK2-DN), or of jnk2(-/-) cardiomyocytes with ad-JNK1-DN, significantly decreased LPS-stimulated mPGES-1 protein synthesis. Similarly, co-infection with ad-JNK1-DN and ad-JNK2-DN attenuated LPS-stimulated mPGES-1 protein synthesis in cardiomyocytes from wild type mice. Targeted deletion of the gene encoding mPGES-1 led to a 3.2-fold decrease in LPS-stimulated PGE(2) release by cardiomyocytes in comparison with wild type cells but had no effect on COX-1, COX-2, mPGES-2, or cytosolic PGES mRNA levels. These studies provide direct evidence that mPGES-1 mRNA levels in cardiomyocytes are augmented by stabilization of mPGES-1 mRNA, that JNK1 or JNK2 can participate in the regulation of mPGES-1 protein synthesis in these cells, and that mPGES-1 catalyzes the majority of LPS-induced PGE(2) biosynthesis by cardiomyocytes.
Norbert Degousee, Denis Angoulvant, Shafie Fazel, Eva Stefanski, Sipra Saha, Karina Iliescu, Thomas F Lindsay, Jason E Fish, Philip A Marsden, Ren-Ke Li, Laurent P Audoly, Per-Johan Jakobsson, Barry B Rubin

1548 related Products with: c-Jun N-terminal kinase-mediated stabilization of microsomal prostaglandin E2 synthase-1 mRNA regulates delayed microsomal prostaglandin E2 synthase-1 expression and prostaglandin E2 biosynthesis by cardiomyocytes.

100ul 100ul100ug100ug100ug100ul 100ul100ug100ug 100ul100ug100ug Lyophilized

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#12898508   // To Up

Jun N-terminal kinase pathway enhances signaling of monocytic differentiation of human leukemia cells induced by 1,25-dihydroxyvitamin D3.

Recent studies revealed that the MEK/ERK module of the mitogen-activated protein kinase (MAPK) signaling cascades is up-regulated in the early stages of 1alpha,25-dihydroxyvitamin D(3) (1,25D(3))-induced monocytic differentiation of human leukemia cells HL60. In the present study, we investigated whether another MAPK module, the JNK pathway, also participates in this form of differentiation. We found that the dependence on the concentration of the inducer, the vitamin-hormone 1,25D(3), in two types of human leukemia cells, HL60 and U937, and the kinetics of monocytic differentiation in HL60 cells, parallel the degree of the activation of the JNK pathway. A blockade of JNK signaling by a stable expression of dominant negative (dn) JNK1 mutant in U937 cells resulted in reduced c-jun phosphorylation, and the differentiation of these cells was markedly decreased. Similarly, inhibition of JNK1 and JNK2 activities by the selective inhibitor SP600125 led to both dose-dependent reduction of c-jun and ATF-2 phosphorylation, and of the differentiation of HL60 cells. In addition, we found that JNK activity is essential for the AP-1 DNA binding induced by 1,25D(3) in HL60 and U937 cells. The results indicate that in cultured human leukemia cells, the JNK pathway participates in the induction of monocytic differentiation by 1,25D(3), probably by activating the AP-1 transcription factor.
Qing Wang, Xuening Wang, George P Studzinski

1358 related Products with: Jun N-terminal kinase pathway enhances signaling of monocytic differentiation of human leukemia cells induced by 1,25-dihydroxyvitamin D3.

5 x 50 ug7 inhibitors1.5x10(6) cells50 ug1.5 x 10^6 cells100ul25 1 Unit100ug Lyophilized2 Pieces/Box1.00 flask 100ul

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