BACKGROUND: Caveolin-1 is a principal component of caveolae membranes in vivo. Although expression of caveolae structure and expression of caveolin family, caveolin-1, -2 and -3, was known in chondrocytes, the functional role of caveolae and caveolins in chondrocytes remains unknown. In this study, we investigated the role of caveolin-1 in articular chondrocytes. METHODS: Rabbit articular chondrocytes were prepared from cartilage slices of 2-week-old New Zealand white rabbits by enzymatic digestion. Caveolin-1 cDNA was transfected to articular chondrocytes using LipofectaminePLUS. The cyclooxygenase-2 (COX-2) expression levels were determined by immunoblot analysis, immunostaining, immunohistochemistry, and prostaglandin E2 (PGE2) assay was used to measure the COX-2 activity. RESULTS: Ectopic expression of caveolin-1 induced COX-2 expression and activity, as indicated by immunoblot analysis and PGE2 assay. And also, overexpression of caveolin-1 stimulated activation of p38 kinase and ERK-1/ -2. Inhibition of p38 kinase and ERK-1/-2 with SB203580 and PD98059, respectively, led to a dose-dependent decrease COX-2 expression and PGE2 production in caveolin-1-transfected cells. CONCLUSION: Taken together, our data suggest that ectopic expression of caveolin-1 contributes to the expression and activity of COX-2 in articular chondrocytes through MAP kinase pathway.
Cartilage ; Caveolae ; Caveolin 1* ; Caveolins ; Chondrocytes* ; Cyclooxygenase 2 ; Digestion ; Dinoprostone ; DNA, Complementary ; Humans ; Immunohistochemistry ; Membranes ; Phosphotransferases* ; Rabbits

Caveolae are specialized lipid rafts that form flask-shaped invaginations of the plasma membrane. Many researches show that caveolae are involved in cell signaling and transport. Caveolin-1 is the major coat protein essential for the formation of caveolae. Recently, several reports indicated that the other caveolae-associated proteins, Cavins, are required for caveola formation and organization. It's worth noting that Cavin-1 could cooperate with Caveolin-1 to accommodate the structural integrity and function of caveolae. Here, we reviewed that the relationship between Cavins and Caveolins and explore the role of them in regulating caveolae.
Animals ; Caveolae ; physiology ; Caveolin 1 ; metabolism ; physiology ; Caveolins ; metabolism ; physiology ; Humans ; Membrane Proteins ; metabolism ; physiology ; RNA-Binding Proteins ; metabolism ; physiology

PURPOSE: To investigate whether up-regulation of the caveolin-1 gene is associated with the resistance to the chemotherapeutic agents in human renal cell carcinomas (HRCC). MATERIALS AND METHODS: Two HRCC cell lines, SN12C and SN12CPM7, with low and high metastatic potentials, respectively, were cultured. Between these two cell lines, the cytotoxicities to doxorubicin, and the expressions of the caveolin-1 gene, were compared using the MTT assay and Northern blot analysis, respectively. A full length of caveolin-1 cDNA was obtained, and inserted into the SN12C to make stable cells expressing the caveolin-1 gene (SN12C/Cav). In these cells, the status of the caveolin-1 expression was evaluated, and the cytotoxicity to doxorubicin or interferon compared to other cell lines. RESULTS: The SN12CPM7 cells were less sensitive to the doxorubicin than the SN12C cells in the cytotoxicity study. The Northern blot analysis revealed that the expression of caveolin-1 was higher in the SN12CPM7 than in the SN12C cells. The expression levels of the caveolin-1 gene in the SN12C/Cav and SN12CPM7 were very similar. The MTT assay, using transfected cell lines, revealed that the SN12C/Cav was more resistant to both the doxorubicin and interferon than the SN12C. CONCLUSIONS: In HRCCs, up-regulation of the caveolin-1 gene may be associated with the change in the biological response to anti-cancer drugs. The induction of the caveolin-1 gene expression may provide the cancer cells with some protection against the action of cytotoxic drugs.
Blotting, Northern ; Carcinoma, Renal Cell ; Caveolin 1* ; Caveolins ; Cell Line ; DNA, Complementary ; Doxorubicin ; Drug Resistance ; Drug Resistance, Multiple* ; Gene Expression ; Humans* ; Interferons ; Up-Regulation*

Exercise training can improve strength and lead to adaptations in the skeletal muscle and nervous systems. Skeletal muscles can develop into two types: fast and slow, depending on the expression pattern of myosin heavy chain (MHC) isoforms. Previous studies reported that exercise altered the distribution of muscle fiber types. It is not currently known what changes in the expression of caveolins and types of muscle fiber occur in response to the intensity of exercise. This study determined the changes in expression of caveolins and MHC type after forced exercise in muscular and non-muscular tissues in rats. A control (Con) group to which forced exercise was not applied and an exercise (Ex) group to which forced exercise was applied. Forced exercise, using a treadmill, was introduced at a speed of 25 m/min for 30 min, 3 times/day (07:00, 15:00, 23:00). Homogenized tissues were applied to extract of total RNA for further gene analysis. The expression of caveolin-3 and MHC2a in the gastrocnemius muscle of female rats significantly increased in the Ex group compared with the Con group (P<0.05). Furthermore, in the gastrocnemius muscle of male rats, the expression of MHC2x was significantly different between the two groups (P<0.05). There was an increased expression in caveolin-3 and a slightly decreased expression in TGFbeta-1 in muscular tissues implicating caveolin-3 influences the expression of MHC isoforms and TGFbeta-1 expression. Eventually, it implicates that caveolin-3 has positive regulatory function in muscle atrophy induced by neural dysfunction with spinal cord injury or stroke.
Animals ; Caveolin 3 ; Caveolins ; Female ; Humans ; Male ; Muscle, Skeletal ; Muscles ; Muscular Atrophy ; Myosin Heavy Chains ; Myosins ; Nervous System ; Protein Isoforms ; Rats ; RNA ; Spinal Cord Injuries ; Stroke

To study the influence of hypercholesterolemia with caveolin-1 on the plasmalemma of vascular endothelium, we used the methods of immunohistochemistry to detect the dynamic changes of caveolin-1 in cultured ECV-304 cells which were stimulated high cholesterol serum and the arterial endothelium of hypercholesterolemia rats. It is resulted that high cholesteorol level can upregulate the expression of caveolin-1 both in vitro and in vivo. In the initial stage of hypercholesterolemia model, the expression of caveolin-1 increased as the time of high cholesterol level added, but in the later period it was decreased slightly.
Animals ; Aorta ; pathology ; Caveolin 1 ; Caveolins ; biosynthesis ; genetics ; Cells, Cultured ; Cholesterol ; blood ; Endothelium, Vascular ; cytology ; metabolism ; Female ; Humans ; Hypercholesterolemia ; metabolism ; Male ; Rabbits ; Rats ; Rats, Sprague-Dawley ; Umbilical Veins ; cytology

The distribution of caveolin isoforms was previouslyevaluated in the retinas of different species, but has notyet been described in the primate retina. In this study, thedistribution of caveolins was assessed via immunochemistryusing isoform-specific antibodies in the retina of the black-and-white ruffed lemur. Here, we report the presence of avariety of caveolin isoforms in many layers of the lemurretina. As normal human retinas were not available forresearch and the retinas of primates are fairly similar tothose of humans, the lemur retina can be utilized as amodel for caveolin distribution in normal humans.
Animals ; Caveolins/*metabolism ; Immunohistochemistry ; Lemur/*metabolism ; Male ; Protein Isoforms ; Retina/*metabolism

Due to the negative autopsy and without cardiac structural abnormalities, unexpected sudden cardiac death （USCD） is always a tough issue for forensic pathological expertise. USCD may be associated with parts of fatal arrhythmic diseases. These arrhythmic diseases may be caused by disorders of cardiac ion channels or channel-related proteins. Caveolin can combine with multiple myocardial ion channel proteins through its scaffolding regions and plays an important role in maintaining the depolarization and repolarization of cardiac action potential. When the structure and function of caveolin are affected by gene mutations or abnormal protein expression, the functions of the regulated ion channels are correspondingly impaired, which leads to the occurrence of multiple channelopathies, arrhythmia or even sudden cardiac death. It is important to study the effects of caveolin on the functions of ion channels for exploring the mechanisms of malignant arrhythmia and sudden cardiac death.
Arrhythmias, Cardiac/physiopathology* ; Autopsy ; Caveolins/metabolism* ; Channelopathies/genetics* ; Death, Sudden, Cardiac/pathology* ; Forensic Pathology ; Humans ; Ion Channels/metabolism* ; Mutation ; Myocardium

OBJECTIVES: To explore the genetic variation sites of caveolin （CAV） and their correlation with sudden unexplained death （SUD）. METHODS: The blood samples were collected from SUD group （71 cases）, coronary artery disease （CAD） group （62 cases） and control group （60 cases）, respectively. The genome DNA were extracted and sequencing was performed directly by amplifying gene coding region and exon-intron splicing region of CAV1 and CAV3 using PCR. The type of heritable variation of CVA was confirmed and statistical analysis was performed. RESULTS: A total of 4 variation sites that maybe significative were identified in SUD group, and two were newfound which were CAV1： c.45C>T （T15T） and CAV1：c.512G>A （R171H）, and two were SNP loci which were CAV1：c.246C>T （rs35242077） and CAV3：c.99C>T （rs1008642） and had significant difference （P<0.05） in allele and genotype frequencies between SUD and control groups. Forementioned variation sites were not found in CAD group. CONCLUSIONS The variants of CAV1 and CAV3 may be correlated with a part of SUD group.
Caveolins/genetics* ; Coronary Artery Disease ; Death, Sudden/etiology* ; Exons ; Genotype ; Humans ; Male ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide

Dysferlin is a plasma membrane protein of skeletal muscle whose deficiency causes Miyoshi myopathy, limb girdle muscular dystrophy 2B and distal anterior compartment myopathy. Recent studies have reported that dysferlin is implicated in membrane repair mechanism and coimmunoprecipitates with caveolin 3 in human skeletal muscle. Caveolin 3 is a principal structural protein of caveolae membrane domains in striated muscle cells and cardiac myocytes. Mutations of caveolin 3 gene (CAV3) cause different diseases and where caveolin 3 expression is defective, dysferlin localization is abnormal. We describe the alteration of dysferlin expression and localization in skeletal muscle from a patient with raised serum creatine kinase (hyperCKaemia), whose reduction of caveolin 3 is caused by a CAV3 P28L mutation. Moreover, we performed a study on dysferlin interaction with caveolin 3 in C2C12 cells. We show the association of dysferlin to cellular membrane of C2C12 myotubes and the low affinity link between dysferlin and caveolin 3 by immunoprecipitation techniques. We also reproduced caveolinopathy conditions in C2C12 cells by a selective p38 MAP kinase inhibition with SB203580, which blocks the expression of caveolin 3. In this model, myoblasts do not fuse into myotubes and we found that dysferlin expression is reduced. These results underline the importance of dysferlin-caveolin 3 relationship for skeletal muscle integrity and propose a cellular model to clarify the dysferlin alteration mechanisms in caveolinopathies.
Animals ; Biopsy ; Caveolin 3 ; Caveolins/*genetics/metabolism ; Cell Line ; Creatine Kinase/*blood ; Enzyme Inhibitors/*pharmacology ; Humans ; Imidazoles/pharmacology ; Insulin/pharmacology ; Membrane Proteins/*metabolism ; Mice ; Mitogen-Activated Protein Kinases/*antagonists & inhibitors/metabolism ; Muscle Proteins/*metabolism ; Muscle, Skeletal/cytology/metabolism ; Mutation/*genetics ; Protein Binding ; Pyridines/pharmacology ; p38 Mitogen-Activated Protein Kinases

The kidney is an important organ for controlling the volume of body fluids, electrolytic balance and excretion/reabsorption of endogenous and exogenous compounds. Among these renal functions, excretion/reabsorption of endogenous and exogenous substance is very important for the maintenance of physiological homeostasis in the body. Recently discovered organic anion transporters (OAT or SLC22A) have important roles for renal functions. It is well known as drug transporter. Several isoforms belong to SLC22A family. They showed different transport substrate spectrums and different localizations within the kidney. Their gene expressions are changed by some stimulus. The functional transport properties are regulated by protein kinase C. In addition, the function of organic anion transporters are also regulated by protein-protein interaction, such as caveolin which is compositional protein of caveolae structure. In this review, we will give an introduction of organic anion transporters and its regulatory mechanisms.
Body Fluids ; Caveolae ; Caveolins* ; Gene Expression ; Homeostasis ; Humans ; Kidney ; Multidrug Resistance-Associated Proteins ; Organic Anion Transporters* ; Protein Isoforms ; Protein Kinase C ; Xenobiotics