Methamphetamine induces autophagy as a pro-survival response against apoptotic endothelial cell death through the Kappa opioid receptor

Ma, J; Wan, J; Meng, J; Banerjee, S; Ramakrishnan, S; Roy, S

We then asked if in response to autophagic stimuli Beclin1 is upregulated through ERK signaling. In total, 0.1 mM, 1 mM, 10 mM and 20 mM PD98059 in a concentration-dependent manner inhibited METH-induced Beclin1 mRNA expression. A total of 20 mM PD98059 significantly inhibited METHinduced Beclin1 mRNA expression compared with METH treatment alone (Figure 4e ). Twenty micrometer PD98059 was used in the following experiments. Twenty micrometer PD98059 also significantly inhibited METH-induced Beclin1 protein expression (Figures 4f and g) . These data suggest that upregulation of Beclin1 is ERK-dependent. In contrast, treatment with METH showed a downregulation of phosphorylated Akt and phosphorylated mTOR, 6 h post treatment (Figures 4h and i) . These results showed that METH induced autophagy in HUVECs by inhibiting the Akt/mTOR pathway and upregulating the ERK1/2 pathway.