Cardiomyoblast caveolin expression: effects of simulated diabetes, α-linolenic acid, and cell signaling pathways.

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 the effects of adenylate cyclase (AC) activation (50 μM forskolin), focal adhesion kinase (FAK) or protein kinase C β ₂ (PKCβ ₂ ) 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 (while reducing expression when combined). Differential control was evident: baseline caveolin-3 was suppressed by FAK/PKCβ ₂ and insensitive to AC activities, with baseline caveolin-1 and -2 suppressed by AC and insensitive to FAK/PKCβ ₂ . Forskolin and ALA selectively preserved caveolin-3 in T2D cells, whereas PKCβ ₂ 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 proinflammatory mediators in T2D cells. In summary, caveolin-1 and -3 are strongly repressed with simulated T2D, with caveolin-3 particularly sensitive to palmitate; intrinsic PKCβ ₂ and FAK activities depress caveolin-3 in healthy and stressed cells; ALA and AC activation and PKCβ ₂ inhibition preserve caveolin-3 under T2D conditions; and caveolin-3 changes with T2D and ALA appear unrelated to inflammatory signaling or extent of apoptosis.