Cationic liposomes suppress intracellular calcium ion concentration increase via inhibition of PI3 kinase pathway in mast cells

• Published in: Biochimica et biophysica acta. Biomembranes 2017-12, Vol.1859 (12), p.2461-2466
• Main Authors: Inoh, Yoshikazu, Haneda, Aki, Tadokoro, Satoshi, Yokawa, Satoru, Furuno, Tadahide
• Format: Article
• Language: English
• Subjects: Allergy; Animals; Calcium - metabolism; Calcium Channels - genetics; Calcium Channels - metabolism; Calcium Signaling; Cations; Cell Line; Cell Membrane - drug effects; Cell Membrane - metabolism; Cell signaling; Cholesterol - analogs & derivatives; Cholesterol - chemistry; Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - metabolism; Gene Expression Regulation; Ion Transport - drug effects; Liposome; Liposomes - chemistry; Liposomes - pharmacology; Mast Cells - cytology; Mast Cells - drug effects; Mast Cells - metabolism; ORAI1 Protein - genetics; ORAI1 Protein - metabolism; Phosphatidylethanolamines - chemistry; Phosphatidylinositol 3-Kinase - antagonists & inhibitors; Phosphatidylinositol 3-Kinase - genetics; Phosphatidylinositol 3-Kinase - metabolism; Phosphorylation - drug effects; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Rats; STIM1; Stromal Interaction Molecule 1 - genetics; Stromal Interaction Molecule 1 - metabolism
• ISSN: 0005-2736; 1879-2642
• DOI: 10.1016/j.bbamem.2017.09.025

Cationic liposomes are commonly used as vectors to effectively introduce foreign genes (antisense DNA, plasmid DNA, siRNA, etc.) into target cells. Cationic liposomes are also known to affect cellular immunocompetences such as the mast cell function in allergic reactions. In particular, we previously showed that the cationic liposomes bound to the mast cell surface suppress the degranulation induced by cross-linking of high affinity IgE receptors in a time- and dose-dependent manner. This suppression is mediated by impairment of the sustained level of intracellular Ca2+ concentration ([Ca2+]i) via inhibition of store-operated Ca2+ entry (SOCE). Here we study the mechanism underlying an impaired [Ca2+]i increase by cationic liposomes in mast cells. We show that cationic liposomes inhibit the phosphorylation of Akt and PI3 kinases but not Syk and LAT. As a consequence, SOCE is suppressed but Ca2+ release from endoplasmic reticulum (ER) is not. Cationic liposomes inhibit the formation of STIM1 puncta, which is essential to SOCE by interacting with Orai1 following the Ca2+ concentration decrease in the ER. These data suggest that cationic liposomes suppress SOCE by inhibiting the phosphorylation of PI3 and Akt kinases in mast cells. [Display omitted] •Cationic liposomes bound to the mast cell surface suppress store-operated Ca2+ entry.•Cationic liposomes inhibit the phosphorylation of Akt and PI3 kinases.•Cationic liposomes did not inhibit the phosphorylation Syk and LAT.•Cationic liposomes inhibit the formation of STIM1 puncta.