| Title |
RLIP76 Depletion Enhances Autophagic Flux in U251 Cells
|
|---|---|
| Published in |
Cellular and Molecular Neurobiology, July 2016
|
| DOI | 10.1007/s10571-016-0410-z |
| Pubmed ID | |
| Authors |
Chenran Zhang, Zheng Cai, Qiang Liang, Qi Wang, Yicheng Lu, Liuhua Hu, Guohan Hu |
| Abstract |
Our previous study showed that RalA-binding protein 1 (RLIP76) is overexpressed in gliomas and is associated with higher tumour grade and decreased patient survival. Furthermore, RLIP76 downregulation increases chemosensitivity of glioma cells to temozolomide by inducing apoptosis. However, other mechanisms underlying RLIP76-associated chemoresistance are unknown. In this study, we investigated the effect of RLIP76 depletion on autophagy. RLIP76 was knocked down in U251 glioma cells using shRNA and autophagy-related proteins, and PI3K/Akt signalling components were evaluated. RLIP76 depletion significantly increased cell autophagy as demonstrated by a significant increase in LC3 II, autophagy protein 5 (ATG-5), and Beclin1, and a decrease in p62 expression levels. Furthermore, RLIP76 knockdown increased autophagic flux in U251 cells as autolysosome numbers increased relative to autophagosome numbers. Autophagy induced by RLIP76 knockdown resulted in increased apoptosis that was independent of temozolomide treatment. Moreover, RLIP76 knockdown decreased PI3K and Akt activation. RLIP76 depletion also resulted in decreased levels of the anti-apoptotic protein Bcl2. LY294002, a PI3K/Akt pathway inhibitor, led to increased autophagy and apoptosis in U251 RLIP76-depleted cells. Therefore, RLIP76 knockdown increased autophagic flux and apoptosis in U251 glioma cells, possibly through inhibition of the PI3K/Akt pathway. Thus, this study provides a novel mechanism for the role of RLIP76 in glioma pathogenesis and chemoresistance. |
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 6 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 3 | 50% |
| Student > Ph. D. Student | 1 | 17% |
| Student > Doctoral Student | 1 | 17% |
| Researcher | 1 | 17% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 2 | 33% |
| Biochemistry, Genetics and Molecular Biology | 2 | 33% |
| Veterinary Science and Veterinary Medicine | 1 | 17% |
| Unknown | 1 | 17% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 31 July 2016.
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#21,358,731
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Outputs of similar age from Cellular and Molecular Neurobiology
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