scholarly journals Tumor Necrosis Factor-α Increases Airway Smooth Muscle Oxidants Production through a NADPH Oxidase-like System to Enhance Myosin Light Chain Phosphorylation and Contractility

2002 ◽  
Vol 277 (25) ◽  
pp. 22814-22821 ◽  
Author(s):  
Gabriel Thabut ◽  
Jamel El-Benna ◽  
Abdoulaye Samb ◽  
Stephano Corda ◽  
Jerôme Megret ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Tumor Necrosis Factor ◽  
Nadph Oxidase ◽  
Light Chain ◽  
Tumor Necrosis ◽  
Myosin Light Chain ◽  
Tumor Necrosis Factor Α ◽  
Myosin Light Chain Phosphorylation ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Dual regulation of tumor necrosis factor-α on myosin light chain phosphorylation in vascular smooth muscle

2015 ◽  
Vol 308 (5) ◽  
pp. H398-H406 ◽  
Author(s):  
Minjie Chen ◽  
Lan Ma ◽  
John E. Hall ◽  
Xuebo Liu ◽  
Zhekang Ying
Keyword(s):  
Smooth Muscle ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Myosin Light Chain ◽  
Tumor Necrosis Factor Α ◽  
Rho Kinase ◽  
Tnf Α ◽  
Factor Α ◽  
Mlc Phosphorylation ◽  
Necrosis Factor

We previously demonstrated that inhibitor κB kinase 2 (IKK2) is a myosin light chain kinase (MLCK). In the present study, we assess whether the prototypical activator of IKK2 tumor necrosis factor-α (TNF-α) regulates the MLCK activity of IKK2 and thus MLC phosphorylation in vascular smooth muscle cells (VSMCs). Kinase activity assay revealed that TNF-α downregulated the MLCK activity of IKK2 in human VSMCs (HVSMCs). However, Western blot analysis did not demonstrate a significant effect of TNF-α on MLC phosphorylation in HVSMCs, and myograph analysis did not reveal a significant effect of TNF-α on the contraction of the aorta from Sprague-Dawley rats and C57Bl/6j mice, suggesting a dual regulation of MLC phosphorylation by TNF-α. Confirming this notion, TNF-α significantly increased MLC phosphorylation in IKK2−/− but not wild-type cells. Furthermore, our results show that TNF-α increased GTP-bound RhoA and MLC phosphatase subunit MYPT1 phosphorylation and markedly reduced MLC phosphorylation in the presence of Rho-kinase inhibitor Y-27632, suggesting that downregulation of MLCK activity of IKK2 by TNF-α is antagonized by simultaneous RhoA/Rho-kinase activation. These results indicate that TNF-α dually regulates MLC phosphorylation through both IKK2 and RhoA/Rho-kinase pathways.

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