Abstract
Caveolae are cholesterol and sphingolipid enriched invaginations of the plasma membrane and are considered a subset of lipid rafts. Caveolins (Cav), the structural proteins essential for caveolae formation, are critically involved in isoflurane‐induced protection of the heart. The noble gas helium (He) mimics isoflurane‐induced cardioprotection but the molecular mechanisms is unknown. We hypothesize that He influences Cav signaling in vivo in mice. C57BL/6 mice inhaled either 70% He (n=8) or 30% oxygen (n=8) for 20 min. Thirty min or 24 h after inhalation hearts were excised. Cav‐1/3 expression was determined after sucrose density fractionation of whole heart tissue. A cholesterol assay of whole heart samples was performed. Serum of these animals was tested for Cav‐1/3.He inhalation decreased Cav‐1 (0.4±0.1) and 3 (0.7±0.1, vs con 1.7±0.3 and 1.2±0.2, respectively, p<0.05) expression after 24 h. Buoyant Cav enriched fractions supported the results showing lower Cav‐1 and 3 levels. Cholesterol levels where significantly lower after He inhalation (1.7±0.1 vs con 2.4±0.3). Subcellular fractions showed lower levels of Cav‐1/3 mostly in cytosolic and mitochondrial fractions. In contrast, Cav‐1/3 showed accumulation in serum in He mice 24 h after exposure.These data indicate that Cav‐1 and 3 are secreted into the blood after He inhalation in mice, suggesting circulation factors may be involved in inducing organ protection by He.
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