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

METH effects on endothelial cells are mediated via Beclin1/Bcl-2 interactions. Beclin1, a novel Bcl-2 homology 3 (BH3) domain-only protein, has an important part in both autophagosome formation and autolysosome fusion. Beclin1 and the class III phosphatidylinositide 3-kinase (PI3K) Vps34 form two distinct complexes. In complex I, which contributes to an autophagosome formation, Atg14L bridges Beclin1 and the Vps34-p150 complex. In complex II, which regulates the vacuolar protein sorting pathway, UV radiation resistance-associated gene product bridges Beclin1 and the Vps34-p150 complex. Bcl-2 family proteins negatively regulate the kinase activity of the Beclin1-Vps34 complex. 15, 16 Thus, accumulation of Beclin1 protein can be used as an indicator of autophagy induction. To further confirm METH-induced autophagy, we measured Beclin1 protein level using confocal microscopy. Our results showed an upregulation of Beclin1 in METH-treated HUVECs (Figure 2a) .