Caveolae and caveolin in transmembrane signaling: Implications for human disease

Schwencke, Carsten; Braun-Dullaeus, Ruediger C.; Wunderlich, Carsten; Strasser, Ruth H.

doi:10.1016/j.cardiores.2005.11.029

Cited by 92 publications

(70 citation statements)

References 87 publications

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“…We next analyzed the effects of ozone inhalation on expression of Cav-1, a membrane scaffolding protein known to negatively regulate PI3K and p44/42 MAPK (Williams and Lisanti, 2004;Schwencke et al, 2006). Western blot analysis revealed that alveolar macrophages from air exposed wild type mice constitutively expressed Cav-1 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Regulation of caveolin-1 expression, nitric oxide production and tissue injury by tumor necrosis factor-α following ozone inhalation

Fakhrzadeh

Laskin²,

Laskin

2008

Toxicology and Applied Pharmacology

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Alveolar macrophages (AM) and inflammatory mediators including nitric oxide and peroxynitrite contribute to ozone-induced lung injury. The generation of these mediators is regulated, in part, by the transcription factor NF-κB. We previously demonstrated a critical role for NF-κB p50 in the ozone-induced injury. In the present studies mechanisms regulating NF-κB activation in the lung after ozone inhalation were analyzed. Treatment of wild type (WT) mice with ozone (0.8 ppm, 3 h) resulted in a rapid increase in NF-κB binding activity in AM, which persisted for at least 12 h. This was not evident in mice lacking TNFα which are protected from ozone-induced injury; there was also no evidence of nitric oxide or peroxynitrite production in lungs from these animals. These data demonstrate that TNFα plays a role in NF-κB activation and toxicity. TNFα signaling involves PI-3-kinase (PI3K)/protein kinase B (PKB), and p44/42 MAP kinase (MAPK) which are important in NF-κB activation. Ozone Inhalation resulted in rapid and transient increases in p44/42 MAPK and PI3K/PKB in AM from WT mice, which was evident immediately after exposure. Caveolin-1, a transmembrane protein that negatively regulates PI3K/PKB and p44/42 MAPK signaling, was downregulated in AM from WT mice after ozone exposure. In contrast, ozone had no effect on caveolin-1, PI3K/PKB or p44/42 MAPK expression in AM from TNFα knockout mice. These data, together with our findings that TNFα suppressed caveolin-1 in cultured AM, suggest that TNFα and downstream signaling mediate activation of NF-κB and the regulation of inflammatory genes important in ozone toxicity, and that this process is linked to caveolin-1.

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Section: Resultsmentioning

confidence: 99%

Regulation of caveolin-1 expression, nitric oxide production and tissue injury by tumor necrosis factor-α following ozone inhalation

Fakhrzadeh

Laskin²,

Laskin

2008

Toxicology and Applied Pharmacology

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“…Thus, there is considerable evidence of caveolin involvement in the modulation of insulin signalling and therefore in the regulation of the intermediary metabolism, which becomes altered in obesity, and associated with metabolic disorders such as insulin resistance and type 2 diabetes [7]. For instance, Cav-3 deficient mice develop late-onset obesity accompanied by insulin resistance in key peripheral tissues and abnormal lipid metabolism [8,9].…”

Section: Introductionmentioning

confidence: 99%

Time‐dependent regulation of muscle caveolin activation and insulin signalling in response to high‐fat diet

et al. 2009

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a b s t r a c tWe studied the effect of high-fat diet on the expression and activation of the three caveolins in rat skeletal muscle and their association with the insulin signalling cascade. Initial response was characterized by increased signalling through Cav-1 and Cav-3 phosphorylation, suggesting that both participate in an initial acute response to the calorie surplus. Afterwards, Cav-1 signalling was slightly reduced, whereas Cav-3 remained active. Late chronic phase signalling through both proteins was impaired inducing a prediabetic state. Summarizing, caveolins seem to mediate a timedependent regulation of insulin cascade in response to high-fat diet in muscle.

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“…The caveolae mediate non-clathrin-dependent endocytosis, and regulate the internalization of particles such as viruses and bacteria (15,16). Caveolin-1 (cav-1), a 21-to 24-kD protein, is a major resident scaffolding protein constituent of caveolae that participates in vesicular trafficking and signal transduction events (14,17,18). Cav-1 has been reported to reduce cell growth and increase apoptosis by inhibiting the activation of growth factor receptors and their downstream signaling pathways (14,17,19).…”

mentioning

confidence: 99%

“…Caveolin-1 (cav-1), a 21-to 24-kD protein, is a major resident scaffolding protein constituent of caveolae that participates in vesicular trafficking and signal transduction events (14,17,18). Cav-1 has been reported to reduce cell growth and increase apoptosis by inhibiting the activation of growth factor receptors and their downstream signaling pathways (14,17,19). In addition, cav-1 negatively regulates smooth muscle cell proliferation (20,21), and arrests mouse embryonic fibroblasts in the G0/G1 phase (22).…”

mentioning

confidence: 99%

Deletion of Caveolin-1 Protects against Oxidative Lung Injury via Up-Regulation of Heme Oxygenase-1

Jin¹,

Kim²,

Chi³

et al. 2008

Am J Respir Cell Mol Biol

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Acute lung injury (ALI) is a major cause of morbidity and mortality in critically ill patients. Hyperoxia causes lung injury in animals and humans, and is an established model of ALI. Caveolin-1, a major constituent of caveolae, regulates numerous biological processes, including cell death and proliferation. Here we demonstrate that caveolin-1-null mice (cav-1 2/2 ) were resistant to hyperoxia-induced death and lung injury. Cav-1 2/2 mice sustained reduced lung injury after hyperoxia as determined by protein levels in bronchoalveolar lavage fluid and histologic analysis. Furthermore, cav-1 2/2 fibroblasts and endothelial cells and cav-1 knockdown epithelial cells resisted hyperoxia-induced cell death in vitro. Basal and inducible expression of the stress protein heme oxygenase-1 (HO-1) were markedly elevated in lung tissue or fibroblasts from cav-1 2/2 mice. Hyperoxia induced the physical interaction between cav-1 and HO-1 in fibroblasts assessed by co-immunoprecipitation studies, which resulted in attenuation of HO activity. Inhibition of HO activity with tin protoporphyrin-IX abolished the survival benefits of cav-1 2/2 cells and cav-1 2/2 mice exposed to hyperoxia. The cav-1 2/2 mice displayed elevated phospho-p38 mitogen-activated protein kinase (MAPK) and p38b expression in lung tissue/cells under basal conditions and during hyperoxia. Treatment with SB202190, an inhibitor of p38 MAPK, decreased hyperoxia-inducible HO-1 expression in wild-type and cav-1 2/2 fibroblasts. Taken together, our data demonstrated that cav-1 deletion protects against hyperoxia-induced lung injury, involving in part the modulation of the HO-1-cav-1 interaction, and the enhanced induction of HO-1 through a p38 MAPK-mediated pathway. These studies identify caveolin-1 as a novel component involved in hyperoxia-induced lung injury.

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Caveolae and caveolin in transmembrane signaling: Implications for human disease

Cited by 92 publications

References 87 publications

Regulation of caveolin-1 expression, nitric oxide production and tissue injury by tumor necrosis factor-α following ozone inhalation

Regulation of caveolin-1 expression, nitric oxide production and tissue injury by tumor necrosis factor-α following ozone inhalation

Time‐dependent regulation of muscle caveolin activation and insulin signalling in response to high‐fat diet

Deletion of Caveolin-1 Protects against Oxidative Lung Injury via Up-Regulation of Heme Oxygenase-1

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