| Inhibition of rapamycin-induced autophagy causes necrotic cell death associated with BAX/BAD mitochondrial translocation. | |
| | |
MedLine Citation:
|
PMID: 22209856 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Rapamycin, a lipophilic macrolide antibiotic, has been found to reduce injury in different models of neurodegenerative disorders. We have previously shown that in neonatal rats subjected to hypoxia-ischemia (HI) the neuroprotective effect of rapamycin was associated with increased autophagy and decreased caspase-3 activation. We show here that the strong reduction of caspase-3 activation after rapamycin was due, at least in part, to its effect on the intrinsic apoptotic mitochondrial pathway because after rapamycin there was a marked reduction of Bax and Bad translocation to mitochondria, cytochrome c release, and caspase-3 activation. Poly (ADP-ribose) polymerase 1 (PARP-1) cleavage and the number of terminal dUDP nick-end labeling (TUNEL)-positive cells were also reduced. To assess how the antiapoptotic effect of rapamycin was linked to the strong autophagy signal induced by the drug, we blocked the formation of autophagosomes with 3-methyladenine (3MA). 3MA administered 10 min after rapamycin, elicited again Bax and Bad translocation to the mitochondria but did not cause cytochrome c release and caspase-3 activation. After 3MA, cells underwent necrotic cell death. These data indicate that rapamycin administered before HI prevents the apoptotic signaling taking place through the mitochondrial pathway. We hypothesize that rapamycin confers a preconditioning-like protection and suggest that caution is necessary before using pharmacological agents targeting autophagy in neuroprotection because they could interfere with endogenous protective mechanisms. |
| | |
Authors:
|
S Carloni; G Buonocore; M Longini; F Proietti; W Balduini |
Related Documents
:
|
16549336 - Acid sphingomyelinase mediated release of ceramide is essential to trigger the mitochon... 10898586 - The putative benzene metabolite 2,3, 5-tris(glutathion-s-yl)hydroquinone depletes gluta... 16971166 - Thrombospondin-1 c-terminal-derived peptide protects thyroid cells from ceramide-induce... 9305886 - Cd95/fas-induced ceramide formation proceeds with slow kinetics and is not blocked by c... 21865716 - Nasal submucosal administration of antigen-presenting cells induces effective immunolog... 15763376 - An herbal formula, herbkines, enhances cytokines production from immune cells. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-12-21 |
Journal Detail:
|
Title: Neuroscience Volume: - ISSN: 1873-7544 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
|
Created Date: 2012-1-2 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 7605074 Medline TA: Neuroscience Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2011. Published by Elsevier Ltd. |
Affiliation:
|
Department of Biomolecular Sciences, University of Urbino "Carlo Bo," Via S. Chiara 27, 61029 Urbino, Italy. |
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: Pilocarpine-induced status epilepticus and subsequent spontaneous seizures: lack of effect on the nu...
Next Document: Giant taro and its relatives: A phylogeny of the large genus Alocasia (Araceae) sheds light on Mioce...