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Cardiomyoblast Caveolin Expression: Effects of Simulated Diabetes, α-linolenic Acid and Cell Signaling Pathways

Cardiomyoblast Caveolin Expression: Effects of Simulated Diabetes, α-linolenic Acid and Cell Signaling Pathways

Jake S Russell, Tia A Griffith, Jason N Peart, John P Headrick

Am J Physiol Cell Physiol. 2020 Apr 29.

PMID: 32348174

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP145915602-A	CGP-53353		145915-60-2	Price

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