BECN1 blocking peptide

The aim of the present study was to measure the expression of microRNA (miRNA) -506-3p in the peripheral blood of patients with hypertension and to determine the biological functions and mechanisms of action of miR-506-3p. A total of 61 patients with primary hypertension were included in the present study. Peripheral blood was collected from all patients, as well as 31 healthy subjects who were included in a control group. The expression of miR-506-3p in peripheral blood was determined by reverse transcription-quantitative polymerase chain reaction. Human umbilical vein endothelial cells (HUVECs) were transfected with miR-506-3p mimics or miR-506-3p inhibitor. The proliferation and migration of HUVECs were determined using cell-counting kit 8 and Transwell assays, respectively. The cell cycle and apoptosis of HUVECs were detected by flow cytometry. The expression of Beclin1 (BECN1) protein, a potential target of miR-506-3p, was measured using western blotting. A dual-luciferase reporter assay was performed to determine the interaction between BECN1 and miR-506-3p. It was demonstrated that miR-506-3p expression in the peripheral blood of patients with patients was upregulated and dependent on the severity of hypertension. miR-506-3p overexpression inhibited the proliferation and migration of HUVECs. In addition, miR-506-3p inhibited the transition from the G1 phase to the S-phase in HUVECs. Overexpression of miR-506-3p promoted the apoptosis of HUVECs. Notably, miR-506-3p downregulated the expression of BECN1 by directly binding to its 3'-untranslated region. The present study demonstrated that miR-506-3p expression is elevated in the peripheral blood of patients with hypertension and is associated with the severity of hypertension. By downregulating BECN1 expression, miR-506-3p aggravates injury in vascular endothelial cells by inhibiting the proliferation and migration of HUVECs, as well as promoting their apoptosis.

We previously showed that autophagy is an important component in human immunodeficiency virus (HIV) replication and in the combined morphine-induced neuroinflammation in human astrocytes and microglia. Here we further studied the consequences of autophagy using glial cells of mice partially lacking the essential autophagy gene Atg6 (Beclin1) exposed to HIV Tat and morphine. Tat is known to cause an inflammatory response, increase calcium release, and possibly interact with autophagy pathway proteins. Following Tat exposure, autophagy-deficient (Becn1(+/-)) glial cells had significantly and consistently reduced levels in the pro-inflammatory cytokine IL-6 and the chemokines RANTES and MCP-1 when compared to Tat-treated cells from control (C57BL/6J) mice, suggesting an association between the inflammatory effects of Tat and Beclin1. Further, differences in RANTES and MCP-1 secretion between C57BL/6J and Becn1(+/-) glia treated with Tat and morphine also suggest a role of Beclin1 in the morphine-induced enhancement. Analysis of autophagy maturation by immunoblot suggests that Beclin1 may be necessary for Tat, and to a lesser extent morphine-induced arrest of the pathway as demonstrated by accumulation of the adaptor protein p62/SQSTM1 in C57BL/6J glia. Calcium release induced by Tat alone or in combination with morphine in C57BL/6J glia was significantly reduced in Becn1(+/-) glia while minimal interactive effect of Tat with morphine in the production of reactive oxygen or nitrogen species was detected in glia derived from Becn1(+/-) or C57BL/6J. Overall, the data establish a role of Beclin1 in Tat and morphine-mediated inflammatory responses and calcium release in glial cells and support the notion that autophagy mediates Tat alone and combined morphine-induced neuropathology.