dc.contributor.author | Russell, Jake S | |
dc.contributor.author | Griffith, Tia A | |
dc.contributor.author | Peart, Jason N | |
dc.contributor.author | Headrick, John P | |
dc.date.accessioned | 2020-05-08T05:00:23Z | |
dc.date.available | 2020-05-08T05:00:23Z | |
dc.date.issued | 2020 | |
dc.identifier.issn | 0363-6143 | |
dc.identifier.doi | 10.1152/ajpcell.00499.2019 | |
dc.identifier.uri | http://hdl.handle.net/10072/393720 | |
dc.description.abstract | Caveolins 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.peerreviewed | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | American Physiological Society | |
dc.relation.ispartofjournal | American Journal of Physiology: Cell Physiology | |
dc.subject.fieldofresearch | Biochemistry and cell biology | |
dc.subject.fieldofresearch | Zoology | |
dc.subject.fieldofresearch | Medical physiology | |
dc.subject.fieldofresearchcode | 3101 | |
dc.subject.fieldofresearchcode | 3109 | |
dc.subject.fieldofresearchcode | 3208 | |
dc.subject.keywords | Cardiomyoblast | |
dc.subject.keywords | Caveolins | |
dc.subject.keywords | Diabetes | |
dc.subject.keywords | Polyunsaturated Fatty Acid | |
dc.subject.keywords | Saturated Fat | |
dc.title | Cardiomyoblast caveolin expression: Effects of simulated diabetes, α-linolenic acid and cell signaling pathways | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dcterms.bibliographicCitation | Russell, 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.updated | 2020-05-07T04:10:05Z | |
dc.description.version | Accepted 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.hasfulltext | Full Text | |
gro.griffith.author | Headrick, John P. | |
gro.griffith.author | Peart, Jason N. | |