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Örtegren (Kugelberg), Unn
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Publications (10 of 15) Show all publications
Nilsson, A., Elander, L., Hallbeck, M., Örtegren (Kugelberg), U., Engblom, D. & Blomqvist, A. (2017). The involvement of prostaglandin E2 in interleukin-1β evoked anorexia is strain dependent. Brain, behavior, and immunity, 60, 27-31
Open this publication in new window or tab >>The involvement of prostaglandin E2 in interleukin-1β evoked anorexia is strain dependent
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2017 (English)In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 60, p. 27-31Article in journal (Refereed) Published
Abstract [en]

From experiments in mice in which the prostaglandin E2 (PGE2) synthesizing enzyme mPGES-1 was genetically deleted, as well as from experiments in which PGE2 was injected directly into the brain, PGE2 has been implicated as a mediator of inflammatory induced anorexia. Here we aimed at examining which PGE2 receptor (EP1–4) that was critical for the anorexic response to peripherally injected interleukin-1β (IL-1β). However, deletion of neither EP receptor in mice, either globally (for EP1, EP2, and EP3) or selectively in the nervous system (EP4), had any effect on the IL-1β induced anorexia. Because these mice were all on a C57BL/6 background, whereas previous observations demonstrating a role for induced PGE2 in IL-1β evoked anorexia had been carried out on mice on a DBA/1 background, we examined the anorexic response to IL-1β in mice with deletion of mPGES-1 on a C57BL/6 background and a DBA/1 background, respectively. We confirmed previous findings that mPGES-1 knock-out mice on a DBA/1 background displayed attenuated anorexia to IL-1β; however, mice on a C57BL/6 background showed the same profound anorexia as wild type mice when carrying deletion of mPGES-1, while displaying almost normal food intake after pretreatment with a cyclooxygenase-2 inhibitor. We conclude that the involvement of induced PGE2 in IL-1β evoked anorexia is strain dependent and we suggest that different routes that probably involve distinct prostanoids exist by which inflammatory stimuli may evoke an anorexic response and that these routes may be of different importance in different strains of mice.

Place, publisher, year, edition, pages
Academic Press, 2017
Keywords
Anorexia, Prostaglandin E2, EP receptors, Interleukin-1, Cyclooxygenase-2, Mice
National Category
Immunology Cell Biology Pharmacology and Toxicology
Identifiers
urn:nbn:se:liu:diva-132639 (URN)10.1016/j.bbi.2016.06.014 (DOI)000391908200004 ()27375005 (PubMedID)
Note

Funding agencies: Swedish Research Council [07879, 20725]; Swedish Cancer Foundation [213/692]; County Council of Ostergotland; Knut and Alice Wallenberg Foundation

Available from: 2016-11-18 Created: 2016-11-18 Last updated: 2019-10-14Bibliographically approved
Fritz, M., Klawonn, A., Nilsson, A., Kumar Singh, A., Zajdel, J., Wilhelms, D., . . . Engblom, D. (2016). Prostaglandin-dependent modulation of dopaminergic neurotransmission elicits inflammation-induced aversion in mice. Journal of Clinical Investigation, 126(2), 695-705
Open this publication in new window or tab >>Prostaglandin-dependent modulation of dopaminergic neurotransmission elicits inflammation-induced aversion in mice
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2016 (English)In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 126, no 2, p. 695-705Article in journal (Refereed) Published
Abstract [en]

Systemic inflammation causes malaise and general feelings of discomfort. This fundamental aspect of the sickness response reduces the quality of life for people suffering from chronic inflammatory diseases and is a nuisance during mild infections like common colds or the flu. To investigate how inflammation is perceived as unpleasant and causes negative affect, we used a behavioral test in which mice avoid an environment that they have learned to associate with inflammation-induced discomfort. Using a combination of cell-type-specific gene deletions, pharmacology, and chemogenetics, we found that systemic inflammation triggered aversion through MyD88-dependent activation of the brain endothelium followed by COX1-mediated cerebral prostaglandin E-2 (PGE(2)) synthesis. Further, we showed that inflammation-induced PGE(2) targeted EP1 receptors on striatal dopamine D1 receptor-expressing neurons and that this signaling sequence induced aversion through GABA-mediated inhibition of dopaminergic cells. Finally, we demonstrated that inflammation-induced aversion was not an indirect consequence of fever or anorexia but that it constituted an independent inflammatory symptom triggered by a unique molecular mechanism. Collectively, these findings demonstrate that PGE(2)-mediated modulation of the dopaminergic motivational circuitry is a key mechanism underlying the negative affect induced by inflammation.

Place, publisher, year, edition, pages
AMER SOC CLINICAL INVESTIGATION INC, 2016
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-126263 (URN)10.1172/JCI83844 (DOI)000370677300029 ()26690700 (PubMedID)
Note

Funding Agencies|European Research Council (ERC); Swedish Medical Research Council; Knut and Alice Wallenberg foundation; Swedish Brain Foundation; County Council of Ostergotland; Swedish Cancer Foundation; Veterans Administration Merit award; NIH [NS33987, NS72337]

Available from: 2016-03-21 Created: 2016-03-21 Last updated: 2019-04-29Bibliographically approved
Wilhelms, D. B., Kirilov, M., Mirrasekhian, E., Eskilsson, A., Örtegren Kugelberg, U., Klar, C., . . . Engblom, D. (2014). Deletion of Prostaglandin E-2 Synthesizing Enzymes in Brain Endothelial Cells Attenuates Inflammatory Fever. Journal of Neuroscience, 34(35), 11684-11690
Open this publication in new window or tab >>Deletion of Prostaglandin E-2 Synthesizing Enzymes in Brain Endothelial Cells Attenuates Inflammatory Fever
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2014 (English)In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 34, no 35, p. 11684-11690Article in journal (Refereed) Published
Abstract [en]

Fever is a hallmark of inflammatory and infectious diseases. The febrile response is triggered by prostaglandin E-2 synthesis mediated by induced expression of the enzymes cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase 1 (mPGES-1). The cellular source for pyrogenic PGE(2) remains a subject of debate; several hypotheses have been forwarded, including immune cells in the periphery and in the brain, as well as the brain endothelium. Here we generated mice with selective deletion of COX-2 and mPGES1 in brain endothelial cells. These mice displayed strongly attenuated febrile responses to peripheral immune challenge. In contrast, inflammation-induced hypoactivity was unaffected, demonstrating the physiological selectivity of the response to the targeted gene deletions. These findings demonstrate that PGE(2) synthesis in brain endothelial cells is critical for inflammation-induced fever.

Place, publisher, year, edition, pages
Society for Neuroscience, 2014
Keywords
COX-2; endothelium; fever; mPGES-1; PGE(2); prostaglandin
National Category
Cell and Molecular Biology Neurosciences
Identifiers
urn:nbn:se:liu:diva-111281 (URN)10.1523/JNEUROSCI.1838-14.2014 (DOI)000341314900017 ()25164664 (PubMedID)
Note

Funding Agencies|Swedish Medical Research Council; Swedish Cancer Foundation; European Research Council; Knut and Alice Wallenberg Foundation; Swedish Brain foundation; County Council of stergotland; Wenner-Gren Fellowship

Available from: 2014-10-14 Created: 2014-10-14 Last updated: 2018-01-11
Matsuwaki, T., Eskilsson, A., Örtegren Kugelberg, U., Jönsson, J.-I. & Blomqvist, A. (2014). Interleukin-1 beta induced activation of the hypothalamus-pituitary-adrenal axis is dependent on interleukin-1 receptors on non-hematopoietic cells. Brain, behavior, and immunity, 40, 166-173
Open this publication in new window or tab >>Interleukin-1 beta induced activation of the hypothalamus-pituitary-adrenal axis is dependent on interleukin-1 receptors on non-hematopoietic cells
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2014 (English)In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 40, p. 166-173Article in journal (Refereed) Published
Abstract [en]

The proinflammatory cytokine interleukin-1 beta (IL-beta) plays a major role in the signal transduction of immune stimuli from the periphery to the central nervous system, and has been shown to be an important mediator of the immune-induced stress hormone release. The signaling pathway by which IL-1 beta exerts this function involves the blood-brain-barrier and induced central prostaglandin synthesis, but the identity of the blood-brain-barrier cells responsible for this signal transduction has been unclear, with both endothelial cells and perivascular macrophages suggested as critical components. Here, using an irradiation and transplantation strategy, we generated mice expressing IL-1 type 1 receptors (IL-1 RI) either in hematopoietic or non-hematopoietic cells and subjected these mice to peripheral immune challenge with IL-beta. Following both intraperitoneal and intravenous administration of IL-beta, mice lacking IL-1R1 in hematopoietic cells showed induced expression of the activity marker c-Fos in the paraventricular hypothalamic nucleus, and increased plasma levels of ACTH and corticosterone. In contrast, these responses were not observed in mice with IL-1R1 expression only in hematopoietic cells. Immunoreactivity for IL-1R1 was detected in brain vascular cells that displayed induced expression of the prostaglandin synthesizing enzyme cyclooxygenase-2 and that were immunoreactive for the endothelial cell marker CD31, but was not seen in cells positive for the brain macrophage marker CD206. These results imply that activation of the HPA-axis by IL-1 beta is dependent on IL-1R1 s on non-hematopoietic cells, such as brain endothelial cells, and that IL-1R1 on perivascular macrophages are not involved.

Place, publisher, year, edition, pages
Elsevier, 2014
Keywords
HPA-axis Corticosterone; ACTH c-Fos Paraventricular nucleus; Chimeric mice; Bone marrow transplantation; Brain endothelial cells; Perivascular macrophages; Cyclooxygenase-2
National Category
Clinical Medicine Cell and Molecular Biology Neurosciences
Identifiers
urn:nbn:se:liu:diva-109874 (URN)10.1016/j.bbi.2014.03.015 (DOI)000339458400019 ()24681250 (PubMedID)
Note

Funding Agencies|Swedish Research Council [61X-078979]; Swedish Cancer Foundation [13 0295]; County Council of Ostergotland; JSPS [H24-451]

Available from: 2014-08-28 Created: 2014-08-28 Last updated: 2018-01-11
Hamzik, N., Tang, Y.-j., Eskilsson, A., Örtegren Kugelberg, U., Ruud, J., Jönsson, J.-I., . . . Nilsberth, C. (2013). Interleukin-6 primarily produced by non-hematopoietic cells mediates the lipopolysaccharide-induced febrile response. Brain, behavior, and immunity, 33, 123-130
Open this publication in new window or tab >>Interleukin-6 primarily produced by non-hematopoietic cells mediates the lipopolysaccharide-induced febrile response
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2013 (English)In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 33, p. 123-130Article in journal (Refereed) Published
Abstract [en]

Interleukin-6 (IL-6) is critical for the lipopolysaccharide (LPS)-induced febrile response. However, the exact source(s) of IL-6 involved in regulating the LPS-elicited fever is still to be identified. One known source of IL-6 is hematopoietic cells, such as monocytes. To clarify the contribution of hematopoietically derived IL-6 to fever, we created chimeric mice expressing IL-6 selectively either in cells of hematopoietic or, conversely, in cells of non-hematopoietic origin. This was performed by extinguishing hematopoietic cells in wild-type (WT) or IL-6 knockout (IL-6 KO) mice by whole-body irradiation and transplanting them with new stem cells. Mice on a WT background but lacking IL-6 in hematopoietic cells displayed normal fever to LPS and were found to have similar levels of IL-6 protein in the cerebrospinal fluid (CSF) and in plasma and of IL-6 mRNA in the brain as WT mice. In contrast, mice on an IL-6 KO background, but with intact IL-6 production in cells of hematopoietic origin, only showed a minor elevation of the body temperature after peripheral LPS injection. While they displayed significantly elevated levels of IL-6 both in plasma and CSF compared with control mice, the increase was modest compared with that seen in LPS injected mice on a WT background, the latter being approximately 20 times larger in magnitude. These results suggest that IL-6 of non-hematopoietic origin is the main source of IL-6 in LPS-induced fever, and that IL-6 produced by hematopoietic cells only plays a minor role.

Place, publisher, year, edition, pages
Elsevier, 2013
Keywords
Interleukin-6, Hematopoietic cells, Bone marrow transplantation, Fever
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-99401 (URN)10.1016/j.bbi.2013.06.006 (DOI)000324788300016 ()
Note

Funding Agencies|Swedish Research Council|33X-0787968X-2053564X-21463|Swedish Cancer Foundation|4095|Swedish Brain Foundation||Tore Nilsson Foundation||Ake Wiberg Foundation||Langmanska Kulturfonden||Lars Hierta Memorial Foundation||Magn. Bergvall Foundation||County Council of Ostergotland||Harald and Greta Jeansson Foundation||Royal Swedish Academy of Sciences||Foundation of the National Board of Health and Welfare||

Available from: 2013-10-17 Created: 2013-10-17 Last updated: 2017-12-06
Vasilache, A.-M., Örtegren Kugelberg, U., Blomqvist, A. & Nilsberth, C. (2013). Minor Changes in Gene Expression in the Mouse Preoptic Hypothalamic Region by Inflammation-Induced Prostaglandin E2. Journal of neuroendocrinology (Print), 25(7), 635-643
Open this publication in new window or tab >>Minor Changes in Gene Expression in the Mouse Preoptic Hypothalamic Region by Inflammation-Induced Prostaglandin E2
2013 (English)In: Journal of neuroendocrinology (Print), ISSN 0953-8194, E-ISSN 1365-2826, Vol. 25, no 7, p. 635-643Article in journal (Refereed) Published
Abstract [en]

We investigated to what extent inflammation-induced prostaglandin E2 (PGE2) regulates gene expression in the central nervous system. Wild-type mice and mice with deletion of the gene encoding microsomal prostaglandin E synthase-1 (mPGES-1), which cannot produce inflammation-induced PGE2, were subjected to peripheral injection of bacterial wall lipopolysaccharide (LPS) and killed after 5 h. The median and medial preoptic nuclei, which are rich in prostaglandin E receptors, were isolated by laser capture microdissection (LCM), and subjected to whole genome microarray analysis. Although the immune stimulus induced robust transcriptional changes in the brain, as seen by a quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) on selected genes, only small PGE2-dependent gene expression changes were observed in the gene array analysis and, for only two genes, a pronounced differential expression between LPS-treated wild-type and mPGES-1 knockout mice could be verified by qRT-PCR. These were Hspa1a and Hspa1b, encoding heat shock proteins, which showed a two- to three-fold higher expression in wild-type mice than in knockout mice after immune challenge. However, the induced expression of these genes was found to be secondary to increased body temperature because they were induced also by cage exchange stress, which did not elicit PGE2 synthesis, and thus were not induced per se by PGE2-elicited transcriptional events. Our findings suggest that inflammation-induced PGE2 has little effect on gene expression in the preoptic region, and that centrally elicited disease symptoms, although PGE2-dependent, occur as a result of regulation of neuronal excitability that is a consequence of intracellular, transcriptional-independent signalling cascades. Our findings also imply that the profound changes in gene expression in the brain that are elicited by peripheral inflammation occur independently of PGE2 via a yet unidentified mechanism.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2013
Keywords
microsomal prostaglandin E synthase-1; prostaglandin E2; fever; preoptic region; laser capture microdissection; whole genome microarray; heat-shock proteins
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-96460 (URN)10.1111/jne.12044 (DOI)000320402900005 ()
Available from: 2013-08-23 Created: 2013-08-20 Last updated: 2017-12-06Bibliographically approved
Fagerholm, S., Örtegren Kugelberg, U., Karlsson, M., Ruishalme, I. & Strålfors, P. (2009). Rapid insulin-dependent endocytosis of the insulin receptor by caveolae in primary adipocytes. PLoS ONE, 4(6), e5985
Open this publication in new window or tab >>Rapid insulin-dependent endocytosis of the insulin receptor by caveolae in primary adipocytes
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2009 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 4, no 6, p. e5985-Article in journal (Refereed) Published
Abstract [en]

Background: The insulin receptor is localized in caveolae and is dependent on caveolae or cholesterol for signaling in adipocytes. When stimulated with insulin, the receptor is internalized. Methodology/Principal Findings: We examined primary rat adipocytes by subcellular fractionation to examine if the insulin receptor was internalized in a caveolae-mediated process. Insulin induced a rapid, t1/2 less than3 min, endocytosis of the insulin receptor in parallel with receptor tyrosine autophosphorylation. Concomitantly, caveolin-1 was phosphorylated at tyrosine(14) and endocytosed. Vanadate increased the phosphorylation of caveolin-1 without affecting insulin receptor phosphorylation or endocytosis. Immunocapture of endosomal vesicles with antibodies against the insulin receptor co-captured caveolin-1 and immunocapture with antibodies against tyrosine(14)-phosphorylated caveolin-1 co-captured the insulin receptor, demonstrating that the insulin receptor was endocytosed together with tyrosine(14)-phosphorylated caveolin-1. By immunogold electron microscopy the insulin receptor and caveolin-1 were colocalized in endosome vesicles that resembled caveosomes. Clathrin was not endocytosed with the insulin receptor and the inhibitor of clathrin-coated pit-mediated endocytosis, chlorpromazine, did not inhibit internalization of the insulin receptor, while transferrin receptor internalization was inhibited. Conclusion: It is concluded that in response to insulin stimulation the autophosphorylated insulin receptor in primary adipocytes is rapidly endocytosed in a caveolae-mediated process, involving tyrosine phosphorylation of caveolin-1.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-21319 (URN)10.1371/journal.pone.0005985 (DOI)
Note
Original Publication: Siri Fagerholm, Unn Örtegren Kugelberg, M. Karlsson, I. Ruishalme and Peter Strålfors, Rapid insulin-dependent endocytosis of the insulin receptor by caveolae in primary adipocytes, 2009, PLoS ONE, (4), 6, e5985. http://dx.doi.org/10.1371/journal.pone.0005985 Available from: 2009-09-30 Created: 2009-09-30 Last updated: 2013-07-08
Örtegren, U., Aboulaich, N., Öst, A. & Strålfors, P. (2007). A new role for caveolae as metabolic platforms. Trends in endocrinology and metabolism, 18(9), 344-349
Open this publication in new window or tab >>A new role for caveolae as metabolic platforms
2007 (English)In: Trends in endocrinology and metabolism, ISSN 1043-2760, E-ISSN 1879-3061, Vol. 18, no 9, p. 344-349Article in journal (Refereed) Published
Abstract [en]

The plasma membrane of cells functions as a barrier to the environment. Caveolae are minute invaginations of the membrane that selectively carry out the exchange of information and materials with the environment, by functioning as organizers of signal transduction and through endocytosis. Recent findings of uptake of different metabolites and of lipid metabolism occurring in caveolae, point to a new general function of caveolae. As gateways for the uptake of nutrients across the plasma membrane, and as platforms for the metabolic conversion of nutrients, especially in adipocytes, caveolae are now emerging as active centers for many aspects of intermediary metabolism, with implications for our understanding of obesity, diabetes and other metabolic disorders.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-40914 (URN)10.1016/j.tem.2007.08.007 (DOI)54533 (Local ID)54533 (Archive number)54533 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13Bibliographically approved
Örtegren Kugelberg, U. (2006). Central adipocyte functions in specialized caveolae. (Doctoral dissertation). Linköping: Institutionen för biomedicin och kirurgi
Open this publication in new window or tab >>Central adipocyte functions in specialized caveolae
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Obesity and overweight is an increasing health problem in the world. Besides reducing quality of life obesity is a great risk factor for development of diseases such as type 2 diabetes, cardiovascular disease, and stroke. The adipose tissue is a flexible organ that grows in size if the body is provided with excess energy. Adipocytes store the excess energy in the form of triacylglycerol. The incorporation of fat is stimulated by insulin, while catecholamines promote hydrolysis of triacylglycerol. In the membrane of adipocytes there are cave-like invaginations, caveolae, where proteins involved in insulin signalling, such as the insulin receptor are located. The focus of this thesis is on the function, and thereby the importance, of adipocytes and caveolae in metabolism.

The lipid content of the plasma membrane and caveolae was analyzed and compared to lipid phases determined in model membranes. The amount of different membrane lipids indicated heterogeneity of the caveolae, since there were not enough of some specific molecules to be present in every caveola. Using density gradient ultra centrifugation three different subclasses of caveolae were identified. These subclasses were named according to their relative densities: very high density caveolae, high density caveolae and low density caveolae. There were clear differences between the classes with regard to the distribution of specific proteins in them. In low density caveolae proteins linked to cholesterol metabolism, scavenger receptor class B type I and CD36, were abundant. Proteins involved in fatty acid metabolism, fatty acid transporter protein 1 and 4, acyl CoA-syntethase, perilipin and hormone sensitive lipase, were localized to high density caveolae. Cholesteryl ester uptake from HDL particles and hydrolysis to cholesterol was found in low density caveolae and the uptake of fatty acids was restricted to high density caveolae. Remarkably, the fatty acids were not only taken up via high density caveolae, but also incorporated into triacylglycerol, diacylglycerol, and phosphatidylcholine. This indicates that the whole machinery for lipid synthesis is located in these caveolae.

In addition to being an energy store the adipose tissue is also an endocrine organ. Several of the secreted proteins affect the metabolism of the body, for instance adiponectin that affects insulin sensitivity. Here adiponectin was located at the plasma membrane to the caveolae, both by biochemical isolation of caveolae and by electron microscopy. Together with earlier findings this indicates that caveolae may be involved in the secretion of adiponectin.

In conclusion, caveolae are involved in central processes such as glucose metabolism and signalling. Herein it is shown that caveolae is involved in the metabolism of fatty acids and cholesterol and may also be involved in the secretion of the metabolic hormone adiponectin. The findings in this thesis together with previous research establish caveolae as metabolic platforms.

Place, publisher, year, edition, pages
Linköping: Institutionen för biomedicin och kirurgi, 2006. p. 50
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 971
Keywords
Obesity, Overweight, Diabetes, Stroke, Cholesterol metabolism, Fatty acids
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-8244 (URN)91-85643-37-8 (ISBN)
Public defence
2006-12-08, Berzeliussalen, Campus US, Linköpings Universitet, Linköping, 13:00 (English)
Opponent
Available from: 2007-02-01 Created: 2007-02-01 Last updated: 2012-10-24Bibliographically approved
Örtegren Kugelberg, U., Yin, L., Öst, A., Karlsson, H., Nyström, F. & Strålfors, P. (2006). Separation and characterization of caveolae subclasses in the plasma membrane of primary adipocytes: segregation of specific proteins and functions. The FEBS Journal, 273(14), 3381-3392
Open this publication in new window or tab >>Separation and characterization of caveolae subclasses in the plasma membrane of primary adipocytes: segregation of specific proteins and functions
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2006 (English)In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 273, no 14, p. 3381-3392Article in journal (Refereed) Published
Abstract [en]

Caveolae are nearly ubiquitous plasma membrane domains that in adipocytes vary in size between 25 and 150 nm. They constitute sites of entry into the cell as well as platforms for cell signalling. We have previously reported that plasma membrane-associated caveolae that lack cell surface access can be identified by electron microscopy. We now report the identification, after density gradient ultracentrifugation, of a subclass of very high-density apparently closed caveolae that were not labelled by cell surface protein labelling of intact cells. These caveolae contained caveolin-1 and caveolin-2. Another class of high-density caveolae contained caveolin-1, caveolin-2 and specifically fatty acid transport protein-1, fatty acid transport protein-4, fatty acyl-CoA synthetase, hormone-sensitive lipase, perilipin, and insulin-regulated glucose transporter-4. This class of caveolae was specialized in fatty acid uptake and conversion to triacylglycerol. A third class of low-density caveolae contained the insulin receptor, class B scavenger receptor-1, and insulin-regulated glucose transporter-4. Small amounts of these proteins were also detected in the high-density caveolae. In response to insulin, the insulin receptor autophosphorylation and the amount of insulin-regulated glucose transporter-4 increased in these caveolae. The molar ratio of cholesterol to phospholipid in the three caveolae classes varied considerably, from 0.4 in very high-density caveolae to 0.9 in low-density caveolae. There was no correlation between the caveolar contents of caveolin and cholesterol. The low-density caveolae, with the highest cholesterol concentration, were particularly enriched with the cholesterol-rich lipoprotein receptor class B scavenger receptor-1, which mediated cholesteryl ester uptake from high-density lipoprotein and generation of free cholesterol in these caveolae, suggesting a specific role in cholesterol uptake/metabolism. These findings demonstrate a segregation of functions in caveolae subclasses.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-35681 (URN)10.1111/j.1742-4658.2006.05345.x (DOI)28128 (Local ID)28128 (Archive number)28128 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13Bibliographically approved
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