Abstract 1332: S100A6 Inhibits S100B and TNFα-Induced Myocyte Apoptosis Via a Pathway That Includes Akt and NF-κB Signaling
S100A6, a member of the S100 family of Ca2+ binding proteins, has been implicated in the regulation of cell growth and proliferation. We have previously shown that the S100A6 is increased post-infarction in vivo and in cultured neonatal rat myocytes in response to growth factors and inflammatory cytokines. In the present study, we demonstrate a 10-fold increase in S100A6 serum levels in a rat model of myocardial infarction 35 days post coronary artery ligation. To determine the functional role of extracellular S100A6, we stimulated rat neonatal cardiac myocyte cultures transfected with the promoter of the transcription factor NF-κB fused to the luciferase reporter with picomolar (1–1000) concentrations of recombinant human S100A6. As evidenced by a decrease in terminal deoxynucleotidyltransferase-mediated UTP end labeling (TUNEL), compared to vehicle control, S1006 at concentrations ≥100 pM attenuated basal myocyte apoptosis (10.1±0.7% vs. 5.3±0.5%, respectively, p<0.05) and inhibited myocyte apoptosis in response to diverse factors including S100B (1 μM, 16.1±0.1.2% vs. 6.4±0.8%, respectively, p<0.05), and TNFα (5 ng/mL, 22.5±2.9% vs. 7.3±1.5%, respectively, p<0.05). Inhibition of myocyte apoptosis by S100A6 was associated with the absence of DNA fragmentation, phosphorylation of Akt, transactivation of NF-κB, increase in Bcl-2 expression and a decrease in Caspase-3 expression and activity. We conclude that extracellular S100A6 may function as a global inhibitor of apoptosis comparable to its putative role as a negative modulator of differentiated cardiac gene expression.