Alternatively spliced tissue factor and full-length tissue factor protect cardiomyocytes against TNF-α-induced apoptosis

摘要: Abstract Tissue Factor (TF) is expressed in various cell types of the heart, such as cardiomyocytes. In addition to its role initiation blood coagulation, TF:FVIIa complex protects cells from apoptosis. There are two isoforms (TF): “full length” (fl)TF—an integral membrane protein, and alternatively spliced (as)TF—a protein that lacks a transmembrane domain can thus be secreted soluble form. Whether asTF or flTF affects apoptosis cardiomyocytes unknown. this study, we examined whether murine TNF-α-induced We used cardiomyocytic HL-1 primary embryonic overexpressed either flTF, stimulated them with TNF-α initiate death. Apoptosis was assessed by annexin-V assay, propidium iodide well activation caspase-3 -9. addition, signaling via integrins, Akt, NFκB Erk1/2, gene-expression Bcl-2 family members were analyzed. here report overexpression reduced phosphatidylserine exposure upon TNF-α-stimulation. led an increased expression phosphorylation up-regulation anti-apoptotic Bcl-xL. The effects mediated αVβ3/Akt/NFκB dependent on Bcl-xL cells. activity also observed using Analogous yet less pronounced sequelae due flTF. Importantly, deficient TF exhibited compared wild type propose protect against specific pathways, family.