The pro-survival role of autophagy depends on Bcl-2 under nutrition stress conditions.
Autophagy can be induced under nutrition stress conditions. Bcl-2 is a pro-survival protein which inhibits apoptosis and autophagy. However, the role of Bcl-2 in autophagy regulation and cell survival under nutrition deprivation has not been fully understood. This study sought to investigate if Bcl-...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3643928?pdf=render |
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| author | Hai-Dong Xu Dan Wu Jin-Hua Gu Jian-Bin Ge Jun-Chao Wu Rong Han Zhong-Qin Liang Zheng-Hong Qin |
| author_facet | Hai-Dong Xu Dan Wu Jin-Hua Gu Jian-Bin Ge Jun-Chao Wu Rong Han Zhong-Qin Liang Zheng-Hong Qin |
| author_sort | Hai-Dong Xu |
| collection | DOAJ |
| description | Autophagy can be induced under nutrition stress conditions. Bcl-2 is a pro-survival protein which inhibits apoptosis and autophagy. However, the role of Bcl-2 in autophagy regulation and cell survival under nutrition deprivation has not been fully understood. This study sought to investigate if Bcl-2 upregulation is essential in limiting autophagic activity and prevent cell death under nutrition deprivation conditions. Autophagic activity was monitored by the changes in GFP-LC3 localization and protein levels of Beclin1, LC3-II, cathepsin D and p62 in neuroblastoma SH-SY5Y cells underwent serum deprivation. Manipulation of Bcl-2 function was achieved with siRNAs and small molecular inhibitors. The cell viability and apoptosis were assessed with MTT assay and Annexin V/PI staining. The results showed that serum starvation increased protein levels of LC3-II and Beclin1 but decreased autophagy substrate p62. Autophagy activation induced by serum deprivation and rapamycin was accompanied by an upregulation of Bcl-2 protein levels. When Bcl-2 was knocked down with siRNA or inhibited with HA 14-1 or ABT-737, serum starvation induced profound cell death and enhanced autophagic flux under nutrition deprivation conditions, while knockdown of autophagic gene Beclin1 or autophagy inhibitors (bafilomycin A1 and E64D), rescued cell death. In contrast, overexpression of Bcl-2 inhibited autophagy and blocked cell death in response to serum deprivation. These data suggest that Bcl-2 plays an essential role in limiting autophagy activation and preventing initiation of programmed cell death. Thus Bcl-2 may be an important mechanism for balancing beneficial and detrimental impacts of autophagy on cell survival. |
| first_indexed | 2024-12-10T10:55:02Z |
| format | Article |
| id | doaj.art-ae68670055334b23a7ed4834a3be120f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T10:55:02Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ae68670055334b23a7ed4834a3be120f2022-12-22T01:51:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0185e6323210.1371/journal.pone.0063232The pro-survival role of autophagy depends on Bcl-2 under nutrition stress conditions.Hai-Dong XuDan WuJin-Hua GuJian-Bin GeJun-Chao WuRong HanZhong-Qin LiangZheng-Hong QinAutophagy can be induced under nutrition stress conditions. Bcl-2 is a pro-survival protein which inhibits apoptosis and autophagy. However, the role of Bcl-2 in autophagy regulation and cell survival under nutrition deprivation has not been fully understood. This study sought to investigate if Bcl-2 upregulation is essential in limiting autophagic activity and prevent cell death under nutrition deprivation conditions. Autophagic activity was monitored by the changes in GFP-LC3 localization and protein levels of Beclin1, LC3-II, cathepsin D and p62 in neuroblastoma SH-SY5Y cells underwent serum deprivation. Manipulation of Bcl-2 function was achieved with siRNAs and small molecular inhibitors. The cell viability and apoptosis were assessed with MTT assay and Annexin V/PI staining. The results showed that serum starvation increased protein levels of LC3-II and Beclin1 but decreased autophagy substrate p62. Autophagy activation induced by serum deprivation and rapamycin was accompanied by an upregulation of Bcl-2 protein levels. When Bcl-2 was knocked down with siRNA or inhibited with HA 14-1 or ABT-737, serum starvation induced profound cell death and enhanced autophagic flux under nutrition deprivation conditions, while knockdown of autophagic gene Beclin1 or autophagy inhibitors (bafilomycin A1 and E64D), rescued cell death. In contrast, overexpression of Bcl-2 inhibited autophagy and blocked cell death in response to serum deprivation. These data suggest that Bcl-2 plays an essential role in limiting autophagy activation and preventing initiation of programmed cell death. Thus Bcl-2 may be an important mechanism for balancing beneficial and detrimental impacts of autophagy on cell survival.http://europepmc.org/articles/PMC3643928?pdf=render |
| spellingShingle | Hai-Dong Xu Dan Wu Jin-Hua Gu Jian-Bin Ge Jun-Chao Wu Rong Han Zhong-Qin Liang Zheng-Hong Qin The pro-survival role of autophagy depends on Bcl-2 under nutrition stress conditions. PLoS ONE |
| title | The pro-survival role of autophagy depends on Bcl-2 under nutrition stress conditions. |
| title_full | The pro-survival role of autophagy depends on Bcl-2 under nutrition stress conditions. |
| title_fullStr | The pro-survival role of autophagy depends on Bcl-2 under nutrition stress conditions. |
| title_full_unstemmed | The pro-survival role of autophagy depends on Bcl-2 under nutrition stress conditions. |
| title_short | The pro-survival role of autophagy depends on Bcl-2 under nutrition stress conditions. |
| title_sort | pro survival role of autophagy depends on bcl 2 under nutrition stress conditions |
| url | http://europepmc.org/articles/PMC3643928?pdf=render |
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