scholarly journals The Deubiquitinating Enzyme USP11 Controls an IκB Kinase α (IKKα)-p53 Signaling Pathway in Response to Tumor Necrosis Factor α (TNFα)

2007 ◽  
Vol 282 (47) ◽  
pp. 33943-33948 ◽  
Author(s):  
Tomoko Yamaguchi ◽  
Junko Kimura ◽  
Yoshio Miki ◽  
Kiyotsugu Yoshida
Keyword(s):  
Tumor Necrosis Factor ◽  
Signaling Pathway ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Deubiquitinating Enzyme ◽  
P53 Signaling ◽  
Iκb Kinase ◽  
Factor Α ◽  
P53 Signaling Pathway ◽  
Necrosis Factor

Adiponectin suppresses IκB kinase activation induced by tumor necrosis factor-α or high glucose in endothelial cells: role of cAMP and AMP kinase signaling

2007 ◽  
Vol 293 (6) ◽  
pp. E1836-E1844 ◽  
Author(s):  
Xiangdong Wu ◽  
Kalyankar Mahadev ◽  
Lauren Fuchsel ◽  
Raogo Ouedraogo ◽  
Shi-qiong Xu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis Factor ◽  
High Glucose ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Amp Kinase ◽  
Inflammatory Signaling ◽  
Iκb Kinase ◽  
Factor Α ◽  
Necrosis Factor

Adiponectin is a protein secreted from adipocytes that exhibits salutary effects in the vascular endothelium by signaling mechanisms that are not well understood. In obesity-related disease states and type 2 diabetes, circulating substances, including tumor necrosis factor-α (TNFα) and high glucose, activate IκB kinase (IKK)β and reduce the abundance of its substrate, inhibitor of κB (IκB)α, leading to nuclear translocation of the transcription factor NF-κB and stimulation of an inflammatory signaling cascade closely associated with endothelial dysfunction. The present study demonstrates that the globular domain of adiponectin (gAd) potently suppresses the activation of IKKβ by either TNFα or high glucose in human umbilical vein endothelial cells and ameliorates the associated loss of IκBα protein. Interestingly, activation of AMP kinase was substantially more effective than cAMP signaling in suppressing high glucose-induced IKKβ activity, whereas both pathways were comparably active in suppressing the TNFα-induced increase in IKKβ. Both cAMP/protein kinase A signaling and activation of the AMP kinase pathway played a role in the suppression by gAd of TNFα- and high glucose-mediated IKKβ activation. These findings support an important role for adiponectin in anti-inflammatory signaling in the endothelium and also imply that multiple pathways are involved in the cellular effects of adiponectin.

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