| PARP and RIP 1 are required for autophagy induced by 11'-deoxyverticillin A, which precedes caspase-dependent apoptosis. | |
| | |
MedLine Citation:
|
PMID: 21460625 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
The epipolythiodioxopiperazines (ETPs) are fungal secondary metabolites proven to trigger both apoptotic and necrotic cell death of tumor cells. However, the underlying mechanism of their regulatory role in macroautophagy and the interplay between autophagy and apoptosis initiated by the ETPs, remain unexplored. In the current work, we found that 11'-deoxyverticillin A (C42), a member of the ETPs, induces autophagosome formation, accumulation of microtubule-associated protein 1 light chain 3-II (LC3-II), and degradation of sequestosome 1 (SQSTM1/p62). In addition, the LC3-II accrual and p62 degradation occur prior to caspase activation, and coincide with PARP activation. Inhibition of autophagy by either chemical inhibitors or by RNA interference single knockdown of essential autophagic genes partially reduces the cell death and the cleavage of both caspase 3 and PARP. Necrostatin-1, a specific inhibitor of necroptosis, inhibits both the augmentation of LC3-II and the cleavage of caspase 3, which was confirmed by depletion of receptor-interacting protein 1 (RIP-1), a crucial necrostatin-1-targeted adaptor kinase mediating cell death and survival. Moreover, inhibition of PARP by either chemical inhibitors or RNA interference provides obvious protection for cell viability and suppresses the LC3-II accretion caused by C42 treatment. Interestingly, double silencing of LC3 and p62 completely suppressed PARP cleavage, and concurrently and maximally augmented the PAR formation induced by C42. Collectively, we have demonstrated that C42 enhances the cellular autophagic process, which requires both PARP and RIP-1 participation, and precedes and may augment the caspase-dependent apoptotic cell death. |
| | |
Authors:
|
Nan Zhang; Yali Chen; Ruixuan Jiang; Erwei Li; Xiuling Chen; Zhijun Xi; Yinglu Guo; Xingzhong Liu; Yuguang Zhou; Yongsheng Che; Xiaojing Yue |
Related Documents
:
|
21255695 - Galactomannan from caesalpinia spinosa induces phenotypic and functional maturation of ... 10698495 - Sensitivity to myc-induced apoptosis is retained in spontaneous and transplanted lympho... 21128005 - Apoptosis and autophagy in the regulation of t lymphocyte function. 21348775 - Aqueous extract of curcuma aromatica induces apoptosis and g2/m arrest in human colon c... 21255695 - Galactomannan from caesalpinia spinosa induces phenotypic and functional maturation of ... 3708905 - Potential role of mononuclear cells infiltration on the autoimmune myocardial dysfunction. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-6-01 |
Journal Detail:
|
Title: Autophagy Volume: 7 ISSN: 1554-8635 ISO Abbreviation: - Publication Date: 2011 Jun |
Date Detail:
|
Created Date: 2011-4-4 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101265188 Medline TA: Autophagy Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
National Research Center of Urological Cancer; Institute of Urology; Peking University First Hospital; Beijing, China. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Do plastids in Dendrobium cv. Lucky Duan petals function similar to autophagosomes and autolysosomes...
Next Document: Unraveling the role of myosin in forming autophagosomes.