The results demonstrated that ERK1/2 signaling pathway was involved in palmitate http://www.selleckchem.com/products/MLN8237.html induced apoptosis in H9c2 cells and adiponectin partially inhibited palmitate induced apoptosis through decreasing the level of phosphorylated ERK1/2. PI3K/Akt and ERK1/2 signaling pathway crosstalk plays a role in regulating adiponectin attenuated palmitate induced apoptosis in H9c2 cells Previous results indicated that 2. 5 ug/mL globular adi ponectin can attenuate palmitate induced apoptosis in H9c2 cells through decreasing the level of p ERK1/2, and simultaneously increasing the level of p Akt. An inter esting question was whether partial recovery of the activity of PI3K/Akt signaling pathway could lead to a decreased activity of ERK1/2 signaling pathway.

Therefore, we fur ther investigated the relationship between ERK1/2 and PI3K/Akt signaling pathway in adiponectin mediated anti apoptosis in H9c2 cells. Cells were exposed to 2. 5 ug/mL globular adiponectin plus palmitate in the absence or the presence of PI3K inhibitor, 10 uM LY294002. Data showed that the level of p ERK1/2 was increased dramat ically. Meanwhile, the level of p Akt was also increased after cells were exposed to palmitate combined with ERK1/2 inhibitor 10 uM U0126. These results indicated that partial inhibition of PI3K/Akt signal ing pathway resulted in activation of ERK1/2 signaling pathway, which attenuated effects of globular adiponectin on anti apoptosis. and partial inhibition of ERK1/2 signal ing pathway resulted in activation of PI3K/Akt signaling pathway and also attenuated palmitate induced apoptosis in H9c2 cells.

Discussion Free fatty acids, such as saturated fatty acids are now recognized as significant contributors to lipotoxicity pathology including insulin resistance, type 2 diabetes, and cardiomyopathy. Palmitate as a kind of satu rated fatty acids can induce apoptosis in diverse cell types, such as cardiomyocytes. Apoptosis or pro grammed cell death is basically cellular suicide which occurs after sufficient cellular damage. Caspase 3, a mem ber of cysteine aspartic proteases that play a central role in the execution of the apoptotic program, exists as an in active 32 kDa proenzyme in normally. The cleavage GSK-3 within the 19 kDa fragment generates a p17 kDa subunit as an activity form. During apoptosis, caspase 3 cleaved the 116 kDa PARP protein to yield a 24 kDa DNA binding fragment and an 89 kDa catalytic fragment. In this study, our results showed that palmitate induced apoptosis through increasing the activ ity of caspase 3 and PARP in H9c2 cells. Adiponectin, an abundant circulating adipokine, is al most exclusively secreted from adipose tissue and exists in the range of 3 30 ug/mL in plasma.