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dc.contributor.authorRussell, Jake S
dc.contributor.authorGriffith, Tia A
dc.contributor.authorPeart, Jason N
dc.contributor.authorHeadrick, John P
dc.date.accessioned2020-05-08T05:00:23Z
dc.date.available2020-05-08T05:00:23Z
dc.date.issued2020
dc.identifier.issn0363-6143
dc.identifier.doi10.1152/ajpcell.00499.2019
dc.identifier.urihttp://hdl.handle.net/10072/393720
dc.description.abstractCaveolins regulate myocardial substrate handling, survival signaling and stress-resistance, however control of expression is incompletely defined. We test how metabolic features of type 2 diabetes (T2D), and modulation of cell signaling, influence caveolins in H9c2 cardiomyoblasts. Cells were exposed to glucose (25 vs. 5 mM), insulin (100 nM) or palmitate (0.1 mM), individually or combined, and effects of adenylate cyclase (AC) activation (50 μM forskolin), focal adhesion kinase (FAK) or protein kinase C b2 (PKCβ2) inhibition (1 μM FAK Inhibitor 14 or CGP-53353, respectively), or the polyunsaturated fatty acid (PUFA) α-linolenic acid (ALA; 10 μM) were tested. Simulated T2D (elevated glucose+insulin+palmitate) depressed caveolin-1 and -3 without modifying caveolin-2. Caveolin-3 repression was primarily palmitate dependent, whereas high glucose (HG) and insulin independently increased caveolin-3 (yet reduced expression when combined). Differential control was evident: baseline caveolin-3 was suppressed by FAK/PKCβ2 and insensitive to AC activities, with baseline caveolin-1 and -2 suppressed by AC and insensitive to FAK/PKCβ2. Forskolin and ALA selectively preserved caveolin-3 in T2D cells, whereas PKCb2 and FAK inhibition increased caveolin-3 under all conditions. Despite preservation of caveolin-3, ALA did not modify nucleosome content (apoptosis marker) or transcription of pro-inflammatory mediators in T2D cells. In summary: caveolin-1 and -3 are strongly repressed with simulated T2D, with caveolin-3 particularly sensitive to palmitate; intrinsic PKCb2 and FAK activities repress caveolin-3 in healthy and stressed cells; ALA, AC activation and PKCβ2 inhibition preserve caveolin-3 under T2D conditions; and caveolin-3 changes with T2D and ALA appear unrelated to inflammatory signaling and extent of apoptosis.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Physiological Society
dc.relation.ispartofjournalAmerican Journal of Physiology: Cell Physiology
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchZoology
dc.subject.fieldofresearchMedical physiology
dc.subject.fieldofresearchcode3101
dc.subject.fieldofresearchcode3109
dc.subject.fieldofresearchcode3208
dc.subject.keywordsCardiomyoblast
dc.subject.keywordsCaveolins
dc.subject.keywordsDiabetes
dc.subject.keywordsPolyunsaturated Fatty Acid
dc.subject.keywordsSaturated Fat
dc.titleCardiomyoblast caveolin expression: Effects of simulated diabetes, α-linolenic acid and cell signaling pathways
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationRussell, JS; Griffith, TA; Peart, JN; Headrick, JP, Cardiomyoblast caveolin expression: Effects of simulated diabetes, α-linolenic acid and cell signaling pathways, American Journal of Physiology: Cell Physiology, 2020
dc.date.updated2020-05-07T04:10:05Z
dc.description.versionAccepted Manuscript (AM)
gro.rights.copyright© 2020 American Physiological Society . This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal website for access to the definitive, published version.
gro.hasfulltextFull Text
gro.griffith.authorHeadrick, John P.
gro.griffith.authorPeart, Jason N.


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