Beclin 1 knockdown retards re-endothelialization and exacerbates neointimal formation via a crosstalk between autophagy and apoptosis

Ye, Lan-Xiang; J, Yu; Liang, Y.Y.; Zeng, Jinsheng; Huang, Ruxun; Liao, Songjie

doi:10.1016/j.atherosclerosis.2014.08.052

Cited by 23 publications

(19 citation statements)

References 35 publications

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“…Beclin-1 is upregulated by certain autophagy-inducing agents, such as the histone deacetylase inhibitor suberoylanilide hydroxamic acid-d5. The findings of the present study are consistent with those reported by Ye et al (35), in which small interfering RNA knockdown of Beclin-1 expression resulted in the inhibition of autophagic cell death.…”

Section: Discussionsupporting

confidence: 93%

Effect and molecular mechanism of mTOR inhibitor rapamycin on temozolomide‑induced autophagic death of U251 glioma cells

Zhou

et al. 2017

Oncol Lett

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Abstract. Glioma is a malignant tumor of the glial tissue that is difficult to excise through surgery, with poor patient prognosis. The use of chemotherapeutic drugs alone to treat glioma following surgery results in a high probability of sequelae, such as tumor recurrence. The present study investigated the effects of a novel treatment combination on glioma cells and determined the molecular mechanisms underlying its action. The effect of temozolomide (TMZ) combined with rapamycin (RAPA) on the TMZ-induced autophagic death of U251 glioma cells was examined. The U251 cell line was treated with TMZ combined with RAPA, and the cell survival rate and half maximal inhibitory concentration (IC 50 ) of TMZ/RAPA was detected using the Cell Counting Kit-8 (CCK-8) assay. Flow cytometry was used to detect changes in cell cycle distribution. The formation of acidic vesicular organelles (AVOs) in the cytoplasm was identified using fluorescence microscopy and quantitatively analyzed. Western blotting was performed to detect the expression levels of autophagy-associated proteins Beclin-1 and microtubule associated protein 1 light chain 3 alpha (MAP1LC3A)-I and II. RAPA (1.25 nM) combined with 5 µM TMZ markedly inhibited U251 cell growth. RAPA reinforced TMZ-induced autophagic death, reducing the IC 50 value of treatment when combined (TMZ alone, 22.5±3.23 µM vs. TMZ and RAPA, 10.35±2.81 µM). Compared with the control group, the proportion of cells in G 2 /M were markedly increased following treatment with TMZ combined with RAPA. Acridine orange staining demonstrated that TMZ combined with RAPA could markedly enhance the generation of intracellular AVOs compared with TMZ or RAPA alone. In addition, Beclin-1 and LC3-II protein expression was markedly increased compared with the control and single treatment groups (P<0.05). The results of the present study indicate that RAPA reinforces TMZ-induced autophagic death of U251 glioma cells, providing a novel therapeutic combination for the treatment of malignant glioma.

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Section: Discussionsupporting

confidence: 93%

Effect and molecular mechanism of mTOR inhibitor rapamycin on temozolomide‑induced autophagic death of U251 glioma cells

Zhou

et al. 2017

Oncol Lett

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“…Subsequently, the sections were stained with secondary rhodamine–conjugated rabbit anti-goat antibody (Proteintech, Wuhan, China) and counterstained with DAPI. To assess reendothelialization, the percentage of the CD34-positive area to the whole luminal surface was measured as described [ 55 ]. For cell immunofluorescence to identify primary cells isolated from HSVs, anti-vWF-FITC (1:100, Abcam) and anti-α-SMA (1:200, Abcam) antibodies were used.…”

Section: Methodsmentioning

confidence: 99%

Upregulation of miR-126-3p promotes human saphenous vein endothelial cell proliferation in vitro and prevents vein graft neointimal formation ex vivo and in vivo

Bing

Meng

et al. 2017

Oncotarget

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Poor long-term patency of vein grafts remains an obstacle in coronary artery bypass grafting (CABG) surgery using an autologous saphenous vein graft. Recent studies have revealed that miR-126-3p promotes vascular integrity and angiogenesis. We aimed to identify the role of miR-126-3p in the setting of vein graft disease and investigate the value of miR-126-3p agomir as a future gene therapy in vein graft failure. Expression analysis of circulating miR-126-3p in plasma from CABG patients established the basic clues that miR-126-3p participates in CABG. The in vitro results indicated that elevated miR-126-3p expression significantly improved proliferation and migration in human saphenous vein endothelial cells (HSVECs) by targeting sprouty-related protein-1 (SPRED-1) and phosphatidylinositol-3-kinase regulatory subunit 2 (PIK3R2), but not in human saphenous vein smooth muscle cells (HSVSMCs). Moreover, the therapeutic potential of miR-126-3p agomir was demonstrated in cultured human saphenous vein (HSV) ex vivo. Finally, local delivery of miR-126-3p agomir was confirmed to enhance reendothelialization and attenuate neointimal formation in a rat vein arterialization model. In conclusion, we provide evidence that upregulation of miR-126-3p by agomir possesses potential clinical value in the prevention and treatment of autologous vein graft restenosis in CABG.

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“…Researchers have identified caspase-3 a predominant effector caspase in apoptosis can cleave Beclin-1 and inhibit autophagy activity [ 72 , 73 ]. For clarity, Beclin-1 and caspase-3 show the signaling connections between autophagy and apoptosis [ 74 ]. Until now, we speculate that UCP2 is crucial for protecting against sepsis-induced cardiomyopathy by promoting cardiomyocytes survival through autophagy induction and apoptosis reduction.…”

Section: Discussionmentioning

confidence: 99%

Melatonin Balance the Autophagy and Apoptosis by Regulating UCP2 in the LPS-Induced Cardiomyopathy

Pan

Zhang

et al. 2018

Molecules

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To explore the mechanism of mitochondrial uncoupling protein 2 (UCP2) mediating the protective of melatonin when septic cardiomyopathy. UCP2 knocked out mice and cardiomyocytes were used to study the effect of melatonin in response to LPS. Indicators of myocardial and mitochondria injury including mitochondrial membrane potential, mitochondrial permeability transition pore, calcium loading, ROS, and ATP detection were assessed. In addition cell viability and apoptosis as well as autophagy-associated proteins were evaluated. Melatonin was able to protect heart function from LPS, which weakened in the UCP2-knockout mice. Consistently, genipin, a pharmacologic inhibitor of UCP2, augmented LPS-induced damage of AC16 cells. In contrast, melatonin upregulated UCP2 expression and protected the cells from the changes in morphology, mitochondrial membrane potential loss, mitochondrial Ca2+ overload, the opening of mitochondrial permeability transition pore, and subsequent increased ROS generation as well as ATP reduction. Mitophagy proteins (Beclin-1 and LC-3β) were increased while apoptosis-associated proteins (cytochrome C and caspase-3) were decreased when UCP2 was up-regulated. In conclusion, UCP2 may play a protecting role against LPS by regulating the balance between autophagy and apoptosis of cardiomyocytes, and by which mechanisms, it may contribute to homeostasis of cardiac function and cardiomyocytes activity. Melatonin may protect cardiomyocytes through modulating UCP2.

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Beclin 1 knockdown retards re-endothelialization and exacerbates neointimal formation via a crosstalk between autophagy and apoptosis

Cited by 23 publications

References 35 publications

Effect and molecular mechanism of mTOR inhibitor rapamycin on temozolomide‑induced autophagic death of U251 glioma cells

Effect and molecular mechanism of mTOR inhibitor rapamycin on temozolomide‑induced autophagic death of U251 glioma cells

Upregulation of miR-126-3p promotes human saphenous vein endothelial cell proliferation in vitro and prevents vein graft neointimal formation ex vivo and in vivo

Melatonin Balance the Autophagy and Apoptosis by Regulating UCP2 in the LPS-Induced Cardiomyopathy

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