title: The pro-survival role of autophagy depends on Bcl-2 under nutrition stress conditions.
abstract: 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.
authors: Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Soochow University School of Pharmaceutical Science, Suzhou, China.
authors: Hai-Dong
authors: HD
authors: Xu
authors: Dan
authors: D
authors: Wu
authors: Jin-Hua
authors: JH
authors: Gu
authors: Jian-Bin
authors: JB
authors: Ge
authors: Jun-Chao
authors: JC
authors: Wu
authors: Rong
authors: R
authors: Han
authors: Zhong-Qin
authors: ZQ
authors: Liang
authors: Zheng-Hong
authors: ZH
authors: Qin
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000235:genetics*; D000071186:Beclin-1; D001578:Benzopyrans / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D002402:Cathepsin D / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D003470:Culture Media / Q000737:chemistry; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D009596:Nitrophenols / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological / Q000235:genetics*; D013449:Sulfonamides / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: C501332:ABT-737; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D001578:Benzopyrans; D001713:Biphenyl Compounds; D003470:Culture Media; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009570:Nitriles; D009596:Nitrophenols; C118585:P62 protein, human; D010879:Piperazines; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D013449:Sulfonamides; D051028:bcl-2-Associated X Protein; C456800:ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate; D002402:Cathepsin D
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