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GW24-e2176 Tongxinluo dose-dependently decreases apoptosis of mesenchymal stem cells under hypoxia and serum deprivation via the MEK/ERK1/2 pathway

Objectives Mesenchymal stem cells (MSCs) are one of the optimal candidates for myocardial infarction. However, the survival ratio of implanted cells in the infarcted heart is low. Tongxinluo (TXL) is a traditional Chinese herbal medicine with multiple cardiovascular protective effects and has been widely used in China to treat patients with coronary heart disease. MEK/ERK pathway plays an important role in mediating cell survival. Therefore, we hypothesised that TXL could promote MSCs survival under hypoxia and serum deprivation (H/SD) via MEK/ERK pathway. Methods MSCs from the Sprague-Dawley rats bone marrow (60-80g, male) were pretreated with TXL (100-800 μg/ml) for 6 hours under H/SD. For inhibitor studies, the cells were preincubated with MEK1/2 inhibitor U0126 (10μM) for 1 hour prior to the addition of TXL (800 μg/ml). Cell apoptosis was assessed using Annexin V/propidine iodine (PI) by flow cytometry, apoptosis related protein bax, cytochrome C and bcl-2 was assessed by western blot. The expression of ERK1/2 and phosphorylation of ERK1/2 were measured by western blot. Results We found that cell apoptosis was significantly upregulated under H/SD conditions compared with the normal. TXL decreases the apoptosis level in a dose-dependent manner especially in the 800mg/ml concentration, demonstrated by reduced apoptosis rate, decreased expression of pro-apoptotic protein bax and cytochrome C and incerased expression of anti-apoptotic protein bcl-2. Further, TXL upregulated the phosphorylation of ERK1/2. And treatment with U0126 attenuated the protective role of TXL coupled with downregulated phosphorylation of ERK1/2. Conclusions TXL protects MSCs from H/SD injury via MEK/ERK1/2 pathway. It provides a further explanation for the protective effects of TXL on MSCs survival.