Disease relevance of Cav

• MCT and MCT+AP rats also developed pulmonary artery medial hypertrophy and RVH, which was normalized by administration of AP-Cav [1].
• Expression of caveolin-1, -2, and -3 in the spinal cords of Lewis rats with experimental autoimmune encephalomyelitis [2].
• Evidence for Na+/Ca2+ exchanger 1 association with caveolin-1 and -2 in C6 glioma cells [3].
• Mice with homozygous deletion of the Cav-1 gene develop PH and right ventricular hypertrophy (RVH) [1].
• Accumulation of molecules involved in alpha1-adrenergic signal within caveolae: caveolin expression and the development of cardiac hypertrophy [4].

Psychiatry related information on Cav

• Caveolin-1, an eNOS inhibitory protein, was upregulated after LPS and chronic alcohol consumption [5].

High impact information on Cav

• In situ coating of the surface of endothelial cells in rat lung with cationic colloidal silica particles was used to separate caveolae from detergent-insoluble membranes rich in glycosyl phosphatidylinositol (GPI)-anchored proteins but devoid of caveolin [6].
• Deficient eNOS activity was associated with a severalfold increase in binding of eNOS with caveolin [7].
• Impaired endothelial nitric oxide synthase activity associated with enhanced caveolin binding in experimental cirrhosis in the rat [7].
• CONCLUSIONS: These studies provide evidence that enhanced expression and interaction of caveolin with eNOS contribute to impaired NO production, reduced NOS activity, and vasoconstriction in the intact cirrhotic liver [7].
• Caveolin transfection results in caveolae formation but not apical sorting of glycosylphosphatidylinositol (GPI)-anchored proteins in epithelial cells [8].

Chemical compound and disease context of Cav

• In conclusion, chronic hypoxia impairs endothelial Ca(2+) metabolism and normal coupling between eNOS and caveolin-1 resulted in eNOS inactivity [9].
• Effect of hereditary obesity on renal expressions of NO synthase, caveolin-1, AKt, guanylate cyclase, and calmodulin [10].
• Nitric oxide down-regulates caveolin-1 expression in rat brains during focal cerebral ischemia and reperfusion injury [11].
• Light-density, Triton X-100-insoluble caveolin-1- and caveolin-2-enriched fractions were obtained after fractionation of rat C6 glioma cells and their separation over 5-40% discontinuous sucrose-density gradients [12].
• After 6 weeks, body weight, blood pressure, creatinine clearance, plasma creatinine, urinary cyclic guanosine monophosphate (cGMP) and immunodetectable levels of Cav-1, sGC and Akt were determined in the renal, aorta, heart and liver tissues from both groups [13].

Biological context of Cav

• Administration of AP-Cav to MCT rats significantly reduced the right ventricular systolic pressure to 30.1 +/- 1.3 mm Hg [1].
• To elucidate the mechanism of nNOS regulation by caveolin, we examined the effects of a caveolin-1 scaffolding domain peptide (CaV1p1; residues (82-101)) on the catalytic activities of wild-type and mutant nNOSs [14].
• These studies provide the first evidence for a direct interaction between dynamin and the caveolin coat, and demonstrate a selectivity of one Dyn2 form toward the caveolae-mediated endocytosis [15].
• In LV tissue of SHR at 18 weeks, caveolin-1 and -3 were similarly decreased, but Hsp90 upregulated, together with a downregulation of eNOS [16].
• Caveolin and GLT-1 gene expression is reciprocally regulated in primary astrocytes: association of GLT-1 with non-caveolar lipid rafts [17].

Anatomical context of Cav

• Caveolin is the principal component of caveolae in vivo [15].
• In the present study, we investigated different modes and mechanisms of caveolin gene regulation in primary rat astrocytes [17].
• METHODS: Histochemical and immunoblotted signals for the NOS isoforms, caveolin and Hsp90 were compared in left ventricle (LV) and aortic or mesenteric vessels between spontaneously hypertensive rats (SHR; 18 and 63 weeks old) and age-matched normotensive Wistar-Kyoto (WKY) rats [16].
• Caveolin-1 was also shown to be present in isolated CNS myelin and oligodendrocyte plasma membranes, where it was partially colocalized with ER [18].
• In summary, PV-1 is developmentally regulated in the rat lung and shows a divergent intracellular localization, with a limited caveolae/Cav-1 colocalization in cultured endothelial cells [19].

Associations of Cav with chemical compounds

• Caveolin-1 expression by means of p38beta mitogen-activated protein kinase mediates the antiproliferative effect of carbon monoxide [20].
• Antagonizing ET-1 effects and blocking its activation in LPS pretreated SECs decreased the LPS-induced overexpression of CAV-1 as well as the inhibition of ET-1-induced NOS activity [21].
• Caveolin-1 and -3, as well as cholesterol, were enriched in the light fractions [22].
• The EGF-R initially binds caveolin, but these two proteins rapidly dissociate following angiotensin II stimulation during the time when EGF-R transactivation is observed [23].
• However, whether ceramide-induced cholesterol displacement is sufficient to alter the protein composition of caveolin-enriched lipid raft membranes is unknown [24].

Physical interactions of Cav

• Caveolin-1 interacts directly with dynamin-2 [15].
• Phosphorylated ERK1/2 localized at focal adhesion complexes along with phospho-caveolin-1, suggesting specific sites of compartmentalization of these signaling molecules [25].
• However, eNOS was tightly coupled with caveolin-1, and was dissociated from heat shock protein 90 or calmodulin in the hypoxic pulmonary artery in either the presence or absence of carbachol [9].
• The purified caveolin-1 binds c-Src, suppressing its autophosphorylation [26].
• In addition, caveolin-1 coimmunoprecipitates with AT1 receptor only on agonist stimulation [27].

Enzymatic interactions of Cav

• Upon E2 treatment, Src kinase is tyrosine phosphorylated, which, in turn, stimulates Src kinase to phosphorylate caveolin-1 [28].

Co-localisations of Cav

• Furthermore, caveolin-3 was colocalized with caveolin-1 in the same caveolae in the apical, lateral, and basal plasma membranes [29].
• Here, we show that eNOS is found in Triton X-100-insoluble membranes prepared from cultured bovine aortic endothelial cells and colocalizes with caveolin, a coat protein of caveolae, in cultured bovine lung microvascular endothelial cells as determined by confocal microscopy [30].
• Double immunogold labelings indicate that furin colocalizes with the caveolae/raft-marker caveolin-1 in the Golgi apparatus and in the basolateral endosomes [31].

Regulatory relationships of Cav

• Alpha-synuclein up-regulates expression of caveolin-1 and down-regulates extracellular signal-regulated kinase activity in B103 neuroblastoma cells: role in the pathogenesis of Parkinson's disease [32].
• Influence of caveolin on constitutively activated recombinant eNOS: insights into eNOS dysfunction in BDL rat liver [33].
• EGF triggers caveolin redistribution from the plasma membrane to the early/sorting endocytic compartment of hepatocytes [34].
• We conclude that, in cholestatic portal hypertension, caveolin may negatively regulate NOS activity in a manner that is reversible by excess calmodulin [35].
• Recruitment of the raft component caveolin-1 was induced at the adhesive contact between the cell surface and TAG-1 beads, indicating that enlarged rafts were generated [36].

Other interactions of Cav

• In the present study, direct interactions of recombinant caveolin-1 with both the oxygenase and reductase domains of nNOS were demonstrated using in vitro binding assays [14].
• Expression of kinase-defective Src mutant interfered with the association between dynamin-2, which caveolin-1 and prevented the uptake of albumin [37].
• In conclusion, this study highlights the occurrence of the reciprocal regulation of caveolin and GLT-1 expression during processes such as astrocyte differentiation via common signaling pathways [17].
• A redistribution of caveolin-3 and a reduction in caveolin-1 and cholesterol levels in the light fractions occurred after 10 min of reperfusion [22].
• In EAE lesions, the immunoreactivity of caveolin-1 was increased in the ependymal cells, some astrocytes, and some inflammatory cells of the spinal cord, while that of caveolin-2 showed an intense immunoreactivity [2].

Analytical, diagnostic and therapeutic context of Cav

• Western blot analysis showed that three isotypes of caveolins including caveolin-1, -2 and -3 increased significantly in the spinal cords of rats during the early stage of EAE, as compared with the levels in control animals (p<0.05); the elevated level of each caveolin persisted during the peak and recovery stage of EAE [2].
• Immunohistochemistry demonstrated that caveolin-1 and -2 were expressed constitutively in the vascular endothelial cells and ependymal cells of the normal rat spinal cord, whereas caveolin-3 was almost exclusively localized in astrocytes [2].
• The ultrastructural localization of eNOS or caveolin-1 was identified by electron microscopy using an immunogold post-embedding method [38].
• Reductions in pulmonary Cav-1 expression have been shown in several animal models of PH and in patients with severe PH [1].
• Our aim was to define caveolin distribution and expression during cardiac postnatal development using immunofluorescence and Western blotting [39].

References