Spatial Compartmentalization of Tumor Necrosis Factor (TNF) Receptor 1-dependent Signaling Pathways in Human Airway Smooth Muscle Cells

Hunter, Irene; Nixon, Graeme F.

doi:10.1074/jbc.m605738200

Cited by 83 publications

(38 citation statements)

References 70 publications

(140 reference statements)

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“…Caveolins do not appear to directly bind to and modulate G protein coupled receptors; however, caveolae and caveolins likely support smooth muscle contraction by regulating G q protein function and phospho-inositide metabolism [56,57]. Moreover, plasma membrane recruitment of RhoA and PKC , which is an important component in Ca 2+ -sensitization that promotes smooth muscle contraction, is dependent on caveolin-1 [58][59][60]. Given the abundance of caveolin-1 and caveolin-2 in contractile airway smooth muscle, and the emerging evidence for a role of these proteins in signaling cascades associated with contractile responses, increasing future investigation is clearly warranted.…”

Section: Caveolae and Caveolins In The Regulation Of Airway Tone Airwmentioning

confidence: 92%

Caveolae and Caveolins in the Respiratory System

Gosens¹,

Mutawe²,

Martin³

et al. 2008

CMM

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Caveolae are flask-shaped invaginations of the plasma membrane that are present in most structural cells. They owe their characteristic Omega-shape to complexes of unique proteins, the caveolins, which indirectly tether cholesterol and sphingolipid-enriched membrane microdomains to the cytoskeleton. Caveolins possess a unique scaffolding domain that anchors receptors, ion channels, second messenger producing enzymes, and effector kinases, thereby sequestering them to caveolae, and modulating cellular signaling and vesicular transport. The lungs express numerous caveolae and high levels of caveolins; therefore they likely play an important role in lung physiology. Indeed, recent and ongoing studies indicate important roles for caveolae and caveolins in the airway epithelium, airway smooth muscle, airway fibroblasts, airway inflammatory cells and the pulmonary vasculature. We review the role of caveolae and caveolins in lung cells and discuss their involvement in cellular signaling associated with asthma, COPD, lung cancer, idiopathic pulmonary fibrosis and pulmonary vascular defects.

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Section: Caveolae and Caveolins In The Regulation Of Airway Tone Airwmentioning

confidence: 92%

Caveolae and Caveolins in the Respiratory System

Gosens¹,

Mutawe²,

Martin³

et al. 2008

CMM

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“…10 Upon interaction with its ligand, TNF-α activates NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway that is involved in apoptosis. 11 The primary role of TNF-α is in the regulation of immune cells, and is able to induce apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Simvastatin Reduces Burn Injury-induced Splenic Apoptosis via Downregulation of the TNF-α/NF-κB Pathway

Zhao

Kaneki

et al. 2015

Annals of Surgery

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Objective Recent studies have suggested that epidermal burn injuries are associated with inflammation and immune dysfunction. Simvastatin has been shown to possess potent anti-inflammatory properties. Thus we hypothesized that simvastatin protects against burn-induced apoptosis in spleen via its anti-inflammatory activity. Methods Wild-type, tumor necrosis factor alpha knockout (TNF-αKO) and NF-κB KO mice were subjected to full-thickness burn injury or sham treatment. The mice then were treated with or without simvastatin and the spleen were harvested to measure the extent of apoptosis. Expression levels of TNF-αand NF-κB were also determined in spleen tissue and serum. Results Burn injury induced significant splenic apoptosis and systemic cytokine production. Simvastatin protected the spleen from apoptosis, reduced cytokine production in the serum and increased the survival rate. Simvastatin decreased burn-induced TNF-αand NF-κB expression in spleen and serum. TNF-αand NF-κB KO mice demonstrated lower levels of apoptosis in spleen in response to burn. Simvastatin did not further decrease burn-caused apoptosis and mortality in either strain of KO mice. Conclusions Simvastatin reduces burn-induced splenic apoptosis via down-regulation of the TNF-α/ NF-κB pathway.

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“…Since this glycosphingolipid is known to co-localize indirectly with TRAF2 in natural membranes, via the TNF-receptor [35], we also characterized the diffusion of TRAF2 in POPC-GUVs containing 1% of GM1. The result obtained demonstrates that the diffusion coefficient (0.4 ± 0.1 µm 2 /s) is indeed of the same order of that found in the rafts-containing GUVs, suggesting that a direct interaction with the ganglioside might take place.…”

Section: Resultsmentioning

confidence: 99%

New insight into the interaction of TRAF2 C-terminal domain with lipid raft microdomains

Ceccarelli

Venere

Nicolai

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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In this study we provide the first evidence of the interaction of a truncated-TRAF2 with lipid rafts microdomains. We have analized this interaction by measuring the diffusion coefficient of the protein in large and giant unilamellar vesicles (LUVs and GUVs, respectively) obtained both from synthetic lipid mixtures and from natural extracts. Steady-state fluorescence measurements performed with synthetic vesicles indicate that this truncated form of TRAF2 displays a tighter binding to raft-like LUVs with respect to the control (POPC-containing LUVs), and that this process depends on the protein oligomeric state. Generalized Polarization measurements and Spectral Phasor Analysis revealed that truncated-TRAF2 affects the membrane fluidity, especially when vesicles are heated up at physiological temperature. The addition of nanomolar concentration of TRAF2 in GUVs also seems to exert a mechanical action, as demonstrated by the formation of intraluminal vesicles, a process in which ganglioside GM1 plays a crucial role.

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Spatial Compartmentalization of Tumor Necrosis Factor (TNF) Receptor 1-dependent Signaling Pathways in Human Airway Smooth Muscle Cells

Abstract: Tumor necrosis factor (TNF)-

Cited by 83 publications

References 70 publications

Caveolae and Caveolins in the Respiratory System

Caveolae and Caveolins in the Respiratory System

Simvastatin Reduces Burn Injury-induced Splenic Apoptosis via Downregulation of the TNF-α/NF-κB Pathway

New insight into the interaction of TRAF2 C-terminal domain with lipid raft microdomains

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