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

Expression of Beclin1 is through the KOR. KOR, is highly expressed on HUVECs. 18 A growing body of evidence indicate that KOR may be involved in the modulation of abuse-related effects of CNS stimulants. 19, 20 Stimulation of KOR decreases acute amphetamine-induced behavior and mRNA expression of neuropeptides in the rat striatum. 21 To determine if KOR has a role in METH-induced autophagy, we examined the effects of the KOR antagonist nor-Binaltorphiminedihydrochloride (nor-BNI) pretreatment on inhibition of METH-induced Beclin1 expression. nor-BNI in a concentration-dependent manner inhibited METH-induced Beclin1 mRNA expression at the indicated concentrations of 1, 10 To confirm the specific role of the KOR antagonist nor-BNI in regulating Beclin1 expression, HUVECs were transfected with scramble siRNA or KOR siRNA. KOR and Beclin1 mRNA expression were detected by real-time PCR analysis. As shown in Figure 3f , KOR siRNA dramatically downregulated KOR mRNA level compared with scramble siRNA-transfected cells. We further examined Beclin1 mRNA expression in response to knockdown of KOR in the presence of METH treatment. As shown in Figure 3g , METH-induced Beclin1 mRNA expression was significantly decreased upon knockdown of KOR.