PI-3K and Akt are mediators of AP-1 induction by 5-MCDE in mouse epidermal Cl41 cells

Li, Jingxia; Chen, Haobin; Tang, Moon‐shong; Shi, Xianglin; Amin, Shantu; Desai, Dhimant; Costa, Max; Huang, Chuanshu

doi:10.1083/jcb.200401004

Cited by 48 publications

(49 citation statements)

References 66 publications

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“…Although it is common to view PI3K-Akt and JNK/p38 as opposing pathways leading to cell survival and apoptosis, respectively (24), JNK activation can also be potentiated through PI3K activation (25,26), as we have demonstrated here. Activation of both PI3K-Akt and JNK pathways has been reported in AD brain tissue, although the downstream consequences of this activity are not clear (27,28).…”

Section: Discussionmentioning

confidence: 64%

Degradation of the Alzheimer Disease Amyloid β-Peptide by Metal-dependent Up-regulation of Metalloprotease Activity

White

Laughton

et al. 2006

Journal of Biological Chemistry

268

296

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Biometals play an important role in Alzheimer disease, and recent reports have described the development of potential therapeutic agents based on modulation of metal bioavailability. The metal ligand clioquinol (CQ) has shown promising results in animal models and small phase clinical trials; however, the actual mode of action in vivo has not been determined. We now report a novel effect of CQ on amyloid ␤-peptide (A␤) metabolism in cell culture. Treatment of Chinese hamster ovary cells overexpressing amyloid precursor protein with CQ and Cu 2؉ or Zn 2؉ resulted in an ϳ85-90% reduction of secreted A␤-(1-40) and A␤-(1-42) compared with untreated controls. Analogous effects were seen in amyloid precursor protein-overexpressing neuroblastoma cells. The secreted A␤ was rapidly degraded through up-regulation of matrix metalloprotease (MMP)-2 and MMP-3 after addition of CQ and Cu 2؉ . MMP activity was increased through activation of phosphoinositol 3-kinase and JNK. CQ and Cu 2؉ also promoted phosphorylation of glycogen synthase kinase-3, and this potentiated activation of JNK and loss of A␤-(1-40). Our findings identify an alternative mechanism of action for CQ in the reduction of A␤ deposition in the brains of CQ-treated animals and potentially in Alzheimer disease patients. Alzheimer disease (AD)4 is characterized by progressive neuronal dysfunction, reactive gliosis, and the formation of amyloid plaques in the brain. The major constituent of AD plaques is the amyloid ␤-peptide (A␤), which is cleaved from the membrane-bound amyloid precursor protein (APP) (1). Aggregated or oligomeric A␤ can induce neurotoxicity through pathways involving free radical production and increased neuronal oxidative stress (2). Among the factors capable of promoting A␤ aggregation in vivo, recent evidence supports a central role for biometals such as Cu 2ϩ and Zn 2ϩ in this process (3). An important factor in controlling A␤ accumulation in AD patients is the activity of A␤-degrading enzymes. Recent studies have identified several candidate proteases that may contribute to catabolism of A␤ in the brain. Neprilysin, insulin-degrading enzyme, angiotensin-converting enzyme, and matrix metalloproteases (MMPs) have all demonstrated A␤-degrading activity in vitro and/or in vivo (4 -6). Reduced activity of these or other A␤-degrading proteases with age may play a role in promoting accumulation and deposition of A␤ in AD patients. Development of strategies to enhance clearance of A␤ may lead to novel therapeutic treatments for AD patients.Promoting A␤ clearance may be achieved through modulating metal sequestration or metal-protein interactions. 5-Chloro-7-iodo-8-hydroxyquinoline or clioquinol (CQ), a disused antibiotic, has received considerable attention as a potential metal ligand in AD and Parkinson disease patients (7-9). Preliminary studies revealed that CQ rapidly and potently dissolved aggregates of synthetic or AD brain-derived A␤ in vitro (10). In subsequent animal studies, a 9-week oral treatment with CQ resulted in a 49% reduction of...

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Section: Discussionmentioning

confidence: 64%

Degradation of the Alzheimer Disease Amyloid β-Peptide by Metal-dependent Up-regulation of Metalloprotease Activity

White

Laughton

et al. 2006

Journal of Biological Chemistry

268

296

View full text Add to dashboard Cite

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“…After the cell density reached 70 -80%, cells were treated as indicated in the figure legends and then extracted with lucif-erase assay lysis buffer (Promega). The luciferase activity was determined with the Dual-Luciferase Reporter Assay System according to the manufacturer's instructions as described (30,31).…”

Section: Methodsmentioning

confidence: 99%

X-linked Inhibitor of Apoptosis Protein (XIAP) Regulation of Cyclin D1 Protein Expression and Cancer Cell Anchorage-independent Growth via Its E3 Ligase-mediated Protein Phosphatase 2A/c-Jun Axis

Cao

Zhang

et al. 2013

Journal of Biological Chemistry

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Background: XIAP is involved in cancer cell proliferation. Results: The deficiency of XIAP E3 ligase inhibits cancer cell anchorage-independent growth, cell cycle transition, and cyclin D1 transcription, which is mediated by its regulation of PP2A catalytic subunit phosphorylation, thereby activating AP-1. Conclusion: XIAP E3 ligase mediates cyclin D1 transcription via PP2A-regulated AP-1 activation. Significance: This study suggests that XIAP E3 ligase can serve as a cancer therapeutic target.

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“…Akt activation is known to influence the activation of the transcription factor NF-κB in other systems [34]. Similarly, the transcription factor AP-1 may also be regulated by Akt1/PKBα [35]. The fibronectin gene promoter has both NF-κB and AP-1 binding sites and may be positively regulated by both transcription factors [36].…”

Section: Discussionmentioning

confidence: 99%

Glucose-induced Akt1 activation mediates fibronectin synthesis in endothelial cells

et al. 2005

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Aims/hypothesis: Increased expression and decreased degradation of extracellular matrix (ECM) proteins are key features of chronic diabetic complications. Fibronectin, a predominant ECM protein, has been shown to be overexpressed in all target organs of diabetic complications and in endothelial cells cultured in high levels of glucose. The present study was designed to elucidate the role of protein kinase B (Akt/PKB) in glucose-induced fibronectin mRNA expression and protein production in vascular endothelial cells. Methods: Human umbilical vein endothelial cells were cultured in the presence of high glucose to study Akt/PKB activation. The upstream and downstream mediators in the Akt/PKB pathway were also investigated using dominant negative transfections and specific inhibitors of signalling pathways. Cells were subjected to real time RT-PCR, western blotting, and confocal microscopy to assess Akt1/PKBα activation and fibronectin mRNA expression and protein production. To detect transcription factor activation, electrophoretic mobility shift assay was carried out. Results: Our data demonstrate that fibronectin mRNA expression and protein production that are induced by high glucose are mediated via activation of Akt/PKB, which is modulated by mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and protein kinase C. Glucose-induced fibronectin mRNA expression and protein production are also mediated by Akt1/PKBα-dependent activation of the transcription factors nuclear factor-κB and activating protein-1. Conclusions/interpretation: Our study provides insight into the mechanical basis of glucoseinduced increases in fibronectin mRNA expression and protein production. High levels of glucose may increase fibronectin mRNA expression and protein production by activating Akt/PKB.

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PI-3K and Akt are mediators of AP-1 induction by 5-MCDE in mouse epidermal Cl41 cells

Cited by 48 publications

References 66 publications

Degradation of the Alzheimer Disease Amyloid β-Peptide by Metal-dependent Up-regulation of Metalloprotease Activity

Degradation of the Alzheimer Disease Amyloid β-Peptide by Metal-dependent Up-regulation of Metalloprotease Activity

X-linked Inhibitor of Apoptosis Protein (XIAP) Regulation of Cyclin D1 Protein Expression and Cancer Cell Anchorage-independent Growth via Its E3 Ligase-mediated Protein Phosphatase 2A/c-Jun Axis

Glucose-induced Akt1 activation mediates fibronectin synthesis in endothelial cells

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